quinua

Déjala en remojo 24 horas sólo con suficiente agua para que queden todos los granitos empapados, es decir, aproximadamente una medida de agua por otra de quinua. Al día siguiente estará hinchada y se habrá iniciado el proceso de germinación, con lo que el valor nutritivo aumenta y, además, con calentar un poco ya se te “cuece”, es decir, ya toma el aspecto típico transparente con un anillito alrededor; en realidad, no hace falta ni hervirla, sólo calentarla un poco; lo de que llegue al punto de ebullición es para evaporar el agua que aún quede, pero puedes escurrirla antes, aunque siempre forma algo de espuma aunque la hayas lavado bien antes de ponerla en remojo y es mejor que esa espuma se evapore con el agua. Así se cuece en pocos segundos, con lo que pierdes menos nutrientes y, por supuesto, ahorras energía. No hacen falta 24 horas para que se hinche y cueza en segundos y, por lo tanto, conserve más nutrientes; bastan pocas horas de remojo; lo de las 24 horas es para que aumente el valor nutritivo al iniciarse el proceso de germinación. Por supuesto, esto es para preparar la quinua por separado, sin verduras, porque si quieres preparar una quinua con verduras también cocinadas, el tiempo de cocción de la quinua es demasiado corto; pero puedes preparar las verduras por separado y luego mezclar.

Primero, revisar a ojo la quinua sobre un plato para separar posibles piedritas ya que es un grano muy chiquito que se puede mezclar con impurezas.

Segundo, lavarla muy bien varias veces batiendo el agua y descartándola.

Tercero, dejarla en remojo una hora o más.

Cuarto, pasado el tiempo de remojo, batirla en el agua otra vez con una espátula o cuchara y cambiarla nuevamente de agua antes de hervirla.

Quinto, colocar abundante agua sin sal a hervir en dos cuencos similares y cuando comienzan a hervir introducir la quinoa en uno de ellos por cinco minutos, colarla tirando el agua y volver a colocarla en el agua hirviendo del otro recipiente durante quince minutos que es lo que tarda en reventar el grano. Dejar reposar unos minutos absorbiendo agua, colar y dejar enfriar.

¿Porqué tanta historia? La quinoa posee saponinas, sustancias tóxicas para los animales y seres humanos con propiedades parecidas a las del jabón, tanto que las mujeres centroamericanas acostumbraban lavarse el cabello o la ropa con el agua del remojo. La toxicidad depende del nivel de saponinas de la variedad que usted vaya a consumir, si es menor al 0,11% son quínoas dulces que son las ideales pero si es mayor al 0,11% son quínoas amargas por la gran cantidad de saponinas y más tóxicas. Yo nunca vi hasta ahora paquetes de quínoa que detallen en la etiqueta el nivel de saponinas de la variedad, así que para evitar irritaciones digestivas y otras más delicadas la única precaución que se recomienda es lavarla muy bien cambiando el agua varias veces como le expliqué arriba.

informe de la FAO sobre los efectos de la saponina 

Déjala en remojo 24 horas sólo con suficiente agua para que queden todos los granitos empapados, es decir, aproximadamente una medida de agua por otra de quinua. Al día siguiente estará hinchada y se habrá iniciado el proceso de germinación, con lo que el valor nutritivo aumenta y, además, con calentar un poco ya se te “cuece”, es decir, ya toma el aspecto típico transparente con un anillito alrededor; en realidad, no hace falta ni hervirla, sólo calentarla un poco; lo de que llegue al punto de ebullición es para evaporar el agua que aún quede, pero puedes escurrirla antes, aunque siempre forma algo de espuma aunque la hayas lavado bien antes de ponerla en remojo y es mejor que esa espuma se evapore con el agua. Así se cuece en pocos segundos, con lo que pierdes menos nutrientes y, por supuesto, ahorras energía. No hacen falta 24 horas para que se hinche y cueza en segundos y, por lo tanto, conserve más nutrientes; bastan pocas horas de remojo; lo de las 24 horas es para que aumente el valor nutritivo al iniciarse el proceso de germinación. Por supuesto, esto es para preparar la quinua por separado, sin verduras, porque si quieres preparar una quinua con verduras también cocinadas, el tiempo de cocción de la quinua es demasiado corto; pero puedes preparar las verduras por separado y luego mezclar.

Primero, revisar a ojo la quinua sobre un plato para separar posibles piedritas ya que es un grano muy chiquito que se puede mezclar con impurezas.

Segundo, lavarla muy bien varias veces batiendo el agua y descartándola.

Tercero, dejarla en remojo una hora o más.

Cuarto, pasado el tiempo de remojo, batirla en el agua otra vez con una espátula o cuchara y cambiarla nuevamente de agua antes de hervirla.

Quinto, colocar abundante agua sin sal a hervir en dos cuencos similares y cuando comienzan a hervir introducir la quinoa en uno de ellos por cinco minutos, colarla tirando el agua y volver a colocarla en el agua hirviendo del otro recipiente durante quince minutos que es lo que tarda en reventar el grano. Dejar reposar unos minutos absorbiendo agua, colar y dejar enfriar.

¿Porqué tanta historia? La quinoa posee saponinas, sustancias tóxicas para los animales y seres humanos con propiedades parecidas a las del jabón, tanto que las mujeres centroamericanas acostumbraban lavarse el cabello o la ropa con el agua del remojo. La toxicidad depende del nivel de saponinas de la variedad que usted vaya a consumir, si es menor al 0,11% son quínoas dulces que son las ideales pero si es mayor al 0,11% son quínoas amargas por la gran cantidad de saponinas y más tóxicas. Yo nunca vi hasta ahora paquetes de quínoa que detallen en la etiqueta el nivel de saponinas de la variedad, así que para evitar irritaciones digestivas y otras más delicadas la única precaución que se recomienda es lavarla muy bien cambiando el agua varias veces como le expliqué arriba.

informe de la FAO sobre los efectos de la saponina 

The amygdalae

The amygdalae (singular: amygdala; /əˈmɪɡdələ/; also corpus amygdaloideum; Latin, from Greek ἀμυγδαλή, amygdalē, ‘almond’, ‘tonsil’[1]) are two almond-shaped groups of nuclei located deep and medially within the temporal lobes of the brain in complex vertebrates, including humans.[2] Shown in research to perform a primary role in the processing of memory, decision-making, andemotional reactions, the amygdalae […]

The amygdalae (singular: amygdala; /??m??d?l?/; also corpus amygdaloideum; Latin, from Greek ????????, amygdal?, ‘almond’, ‘tonsil’[1]) are two almond-shaped groups of nuclei located deep and medially within the temporal lobes of the brain in complex vertebrates, including humans.[2] Shown in research to perform a primary role in the processing of memory, decision-making, andemotional reactions, the amygdalae are considered part of the limbic system.[3]

Amygdalar development

There is considerable growth within the first few years of structural development in both male and female amygdalae. Within this early period, female limbic structures grow at a more rapid pace than do males. Amongst female subjects, the amygdala reaches its full growth potential approximately 1.5 years before the peak of male development. The structural development of the male amygdala occurs over a longer period than in women. Despite the early development of female amygdalae, they reach their growth potential sooner than males, whose amygdalae continue to develop. The larger relative size of the male amygdala may be attributed to this extended developmental period.

In addition to longer periods of development, other neurological and hormonal factors may contribute to sex-specific developmental differences. The amygdala is rich in androgen receptors – nuclear receptors that bind to testosterone. Androgen receptors play a role in the DNA binding that regulates gene expression. Though testosterone is present within the female hormonal systems, women have lower levels of testosterone than men. The abundance of testosterone in the male hormonal system may contribute to development. In addition, the grey matter volume on the amygdala is predicted by testosterone levels, which may also contribute to the increased mass of the male amygdala.

In addition to sex differences, there are observable developmental differences between the right and left amygdala in both males and females. The left amygdala reaches its developmental peak approximately 1.5–2 years prior to the right amygdala. Despite the early growth of the left amygdala, the right increases in volume for a longer period of time. The right amygdala is associated with response to fearful stimuli as well as face recognition. It is inferred that the early development of the left amygdala functions to provide infants the ability to detect danger.[12]

In childhood, the amygdala is found to react differently to same-sex versus opposite-sex individuals. This reactivity decreases until a person enters adolescence, where it increases dramatically at puberty.[13]

Gender distinction

The amygdala is one of the best-understood brain regions with regard to differences between the sexes. Larger male than female amygdalae have been demonstrated in children ages 7–11,[14] in adult humans,[15] and in adult rats.[16]

In addition to size, other differences between men and women exist with regards to the amygdala. Subjects’ amygdala activation was observed when watching a horror film andsubliminal stimuli. The results of the study showed a different lateralization of the amygdala in men and women. Enhanced memory for the film was related to enhanced activity of the left, but not the right, amygdala in women, whereas it was related to enhanced activity of the right, but not the left, amygdala in men.[17] One study found evidence that on average, women tend to retain stronger memories for emotional events than men.[18]

The right amygdala is also linked with taking action as well as being linked to negative emotions,[19] which may help explain why males tend to respond to emotionally stressful stimuli physically. The left amygdala allows for the recall of details, but it also results in more thought rather than action in response to emotionally stressful stimuli, which may explain the absence of physical response in women.

Emotional learning

In complex vertebrates, including humans, the amygdalae perform primary roles in the formation and storage of memories associated with emotional events. Research indicates that, during fear conditioning, sensory stimuli reach the basolateral complexes of the amygdalae, particularly the lateral nuclei, where they form associations with memories of the stimuli. The association between stimuli and the aversive events they predict may be mediated by long-term potentiation,[22][23] a sustained enhancement of signaling between affected neurons.[24] There have been studies that show that damage to the amygdala can interfere with memory that is strengthened by emotion. One study examined a patient with bilateral degeneration of the amygdala. He was told a violent story accompanied by matching pictures and was observed based on how much he could recall from the story. The patient had less recollection of the story than patients with functional amygdala, showing that the amygdala has a strong connection with emotional learning.[25]

Memories of emotional experiences imprinted in reactions of synapses in the lateral nuclei elicit fear behavior through neuronal connections with the central nucleus of the amygdalae and the bed nuclei of the stria terminalis (BNST). The axon terminals from sensory neurons form synapses with dendritic spines on neurons from the central nucleus.[26] The central nuclei are involved in the genesis of many fear responses such as defensive behavior (freezing or escape responses), autonomic nervous system responses (changes in blood pressure and heart rate/tachycardia), neuroendocrine responses (stress-hormone release), etc. Damage to the amygdalae impairs both the acquisition and expression of Pavlovian fear conditioning, a form of classical conditioning of emotional responses.[24]

The amygdalae are also involved in appetitive (positive) conditioning. It seems that distinct neurons respond to positive and negative stimuli, but there is no clustering of these distinct neurons into clear anatomical nuclei.[27][28] However, lesions of the central nucleus in the amygdala have been shown to reduce appetitive learning in rats. Lesions of the basolateral regions do not exhibit the same effect.[29] Research like this indicates that different nuclei within the amygdala have different functions in appetitive conditioning.[30][31]

Memory modulation

The amygdala is also involved in the modulation of memory consolidation. Following any learning event, the long-term memory for the event is not formed instantaneously. Rather, information regarding the event is slowly assimilated into long-term (potentially lifelong) storage over time, possibly via long-term potentiation. Recent studies suggest that the amygdala regulates memory consolidation in other brain regions. Also, fear conditioning, a type of memory that is impaired following amygdala damage, is mediated in part by long-term potentiation.[22][23]

During the consolidation period, the memory can be modulated. In particular, it appears that emotional arousal following the learning event influences the strength of the subsequent memory for that event. Greater emotional arousal following a learning event enhances a person’s retention of that event. Experiments have shown that administration of stress hormones to mice immediately after they learn something enhances their retention when they are tested two days later.[32]

The amygdala, especially the basolateral nuclei, are involved in mediating the effects of emotional arousal on the strength of the memory for the event, as shown by many laboratories including that of James McGaugh. These laboratories have trained animals on a variety of learning tasks and found that drugs injected into the amygdala after training affect the animals’ subsequent retention of the task. These tasks include basic classical conditioning tasks such as inhibitory avoidance, where a rat learns to associate a mild footshock with a particular compartment of an apparatus, and more complex tasks such as spatial or cued water maze, where a rat learns to swim to a platform to escape the water. If a drug that activates the amygdalae is injected into the amygdalae, the animals had better memory for the training in the task.[33] If a drug that inactivates the amygdalae is injected, the animals had impaired memory for the task.

Buddhist monks who do compassion meditation have been shown to modulate their amygdala, along with their temporoparietal junction and insula, during their practice.[34] In anfMRI study, more intensive insula activity was found in expert meditators than in novices.[35] Increased activity in the amygdala following compassion-oriented meditation may contribute to social connectedness.[36]

Amygdala activity at the time of encoding information correlates with retention for that information. However, this correlation depends on the relative “emotionalness” of the information. More emotionally arousing information increases amygdalar activity, and that activity correlates with retention. Amygdala neurons show various types of oscillationduring emotional arousal, such as theta activity. These synchronized neuronal events could promote synaptic plasticity (which is involved in memory retention) by increasing interactions between neocortical storage sites and temporal lobe structures involved in declarative memory.[37]

Research using Rorschach test blot 03 finds that the number of unique responses to this random figure links to larger sized amygdalae. The researchers note, “Since previous reports have indicated that unique responses were observed at higher frequency in the artistic population than in the nonartistic normal population, this positive correlation suggests that amygdalar enlargement in the normal population might be related to creative mental activity.”[38]

Neuropsychological correlates of amygdala activity

Early research on primates provided explanations as to the functions of the amygdala, as well as a basis for further research. As early as 1888, rhesus monkeys with a lesioned temporal cortex (including the amygdala) were observed to have significant social and emotional deficits.[39] Heinrich Klüver and Paul Bucy later expanded upon this same observation by showing that large lesions to the anterior temporal lobe produced noticeable changes, including overreaction to all objects, hypoemotionality, loss of fear, hypersexuality, and hyperorality, a condition in which inappropriate objects are placed in the mouth. Some monkeys also displayed an inability to recognize familiar objects and would approach animate and inanimate objects indiscriminately, exhibiting a loss of fear towards the experimenters. This behavioral disorder was later named Klüver-Bucy syndrome accordingly,[40] and later research proved it was specifically due to amygdala lesions. Monkey mothers who had amygdala damage showed a reduction in maternal behaviors towards their infants, often physically abusing or neglecting them.[41] In 1981, researchers found that selective radio frequency lesions of the whole amygdala caused Klüver-Bucy syndrome.[42]

With advances in neuroimaging technology such as MRI, neuroscientists have made significant findings concerning the amygdala in the human brain. A variety of data shows the amygdala has a substantial role in mental states, and is related to many psychological disorders. Some studies have shown children with anxiety disorders tend to have a smaller left amygdala. In the majority of the cases, there was an association between an increase in the size of the left amygdala with the use of SSRIs (antidepressant medication) or psychotherapy. The left amygdala has been linked to social anxiety, obsessive and compulsive disorders, and post traumatic stress, as well as more broadly to separation and general anxiety.[43] In a 2003 study, subjects with borderline personality disorder showed significantly greater left amygdala activity than normal control subjects. Some borderline patients even had difficulties classifying neutral faces or saw them as threatening.[44] Individuals with psychopathy show reduced autonomic responses, relative to comparison individuals, to instructed fear cues.[45] In 2006, researchers observed hyperactivity in the amygdala when patients were shown threatening faces or confronted with frightening situations. Patients with more severe social phobia showed a correlation with increased response in the amygdala.[46] Similarly, depressed patients showed exaggerated left amygdala activity when interpreting emotions for all faces, and especially for fearful faces. Interestingly, this hyperactivity was normalized when patients were administered antidepressant medication.[47] By contrast, the amygdala has been observed to respond differently in people with bipolar disorder. A 2003 study found that adult and adolescent bipolar patients tended to have considerably smaller amygdala volumes and somewhat smaller hippocampal volumes.[48] Many studies have focused on the connections between the amygdala and autism.[49]

Studies in 2004 and 2006 showed that normal subjects exposed to images of frightened faces or faces of people from another race will show increased activity of the amygdala, even if that exposure is subliminal.[50][51] However, the amygdala is not necessary for the processing of fear-related stimuli, since persons in whom it is bilaterally damaged show rapid reactions to fearful faces, even in the absence of a functional amygdala.[52]

Recent research suggests that parasites, in particular toxoplasma, form cysts in the brain of rats, often taking up residence in the amygdala. This may provide clues as to how specific parasites may contribute to the development of disorders, including paranoia.[53]

Future studies have been proposed to address the role of the amygdala in positive emotions, and the ways in which the amygdala networks with other brain regions.[54]

Sexual orientation

Recent studies have suggested possible correlations between brain structure, including differences in hemispheric ratios and connection patterns in the amygdala, and sexual orientation. Homosexual men tend to exhibit more female-like patterns in the amygdala than heterosexual males do, just as homosexual females tend to show more male-like patterns in the amygdala than heterosexual women do. It was observed that amygdala connections were more widespread from the left amygdala in homosexual males, as is also found in heterosexual females. Amygdala connections were more widespread from the right amygdala in homosexual females, as in heterosexual males.[55][55][56]

Social interaction

Amygdala volume correlates positively with both the size (the number of contacts a person has) and the complexity (the number of different groups to which a person belongs) of social networks.[57][58] Individuals with larger amygdalae had larger and more complex social networks. They were also better able to make accurate social judgments about other persons’ faces.[59] The amygdala’s role in the analysis of social situations stems specifically from its ability to identify and process changes in facial features. It does not, however, process the direction of the gaze of the person being perceived.[60][61]

The amygdala is also thought to be a determinant of the level of a person’s emotional intelligence. It is particularly hypothesized that larger amygdalae allow for greater emotional intelligence, enabling greater societal integration and cooperation with others.[62]

The amygdala processes reactions to violations concerning personal space. These reactions are absent in persons in whom the amygdala is damaged bilaterally.[63]Furthermore, the amygdala is found to be activated in fMRI when people observe that others are physically close to them, such as when a person being scanned knows that an experimenter is standing immediately next to the scanner, versus standing at a distance.[63]

Aggression

Animal studies have shown that stimulating the amygdala appears to increase both sexual and aggressive behavior. Likewise, studies using brain lesions have shown that harm to the amygdala may produce the opposite effect. Thus, it appears that this part of the brain may play a role in the display and modulation of aggression.[64]

Fear

There are cases of human patients with focal bilateral amygdala lesions, due to the rare genetic condition Urbach-Wiethe disease.[65][66] Such patients fail to exhibit fear-related behaviors, leading one, Patient S.M., to be dubbed the “woman with no fear”. This finding reinforces the conclusion that the amygdala “plays a pivotal role in triggering a state of fear”.[67]

Alcoholism and binge drinking

The amygdala appears to play a role in binge drinking, being damaged by repeated episodes of intoxication and withdrawal.[68] Alcoholism is associated with dampened activation in brain networks responsible for emotional processing[clarification needed], including the amygdala.[69] Protein kinase C-epsilon in the amygdala is important for regulating behavioral responses to morphine, ethanol, and controlling anxiety-like behavior. The protein is involved in controlling the function of other proteins and plays a role in development of the ability to consume a large amount of ethanol.[70][71]

Anxiety

There may also be a link between the amygdala and anxiety.[72] In particular, there is a higher prevalence of females that are affected by anxiety disorders. In an experiment,degu pups were removed from their mother but allowed to hear her call. In response, the males produced increased serotonin receptors in the amygdala but females lost them. This led to the males being less affected by the stressful situation.

The clusters of the amygdala are activated when an individual expresses feelings of fear or aggression. This occurs because the amygdala is the primary structure of the brain responsible for flight or fight response. Anxiety and panic attacks can occur when the amygdala senses environmental stressors that stimulate fight or flight response.

The amygdala is directly associated with conditioned fear. Conditioned fear is the framework used to explain the behavior produced when an originally neutral stimulus is consistently paired with a stimulus that evokes fear. The amygdala represents a core fear system in the human body, which is involved in the expression of conditioned fear. Fear is measured by changes in autonomic activity including increased heart rate, increased blood pressure, as well as in simple reflexes such as flinching or blinking.

The central nucleus of the amygdala has direct correlations to the hypothalamus and brainstem – areas directly related to fear and anxiety. This connection is evident from studies of animals that have undergone amygdalae removal. Such studies suggest that animals lacking an amygdala have less fear expression and indulge in non-species-like behavior. Many projection areas of the amygdala are critically involved in specific signs that are used to measure fear and anxiety.

Mammals have very similar ways of processing and responding to danger. Scientists have observed similar areas in the brain – specifically in the amygdala – lighting up or becoming more active when a mammal is threatened or beginning to experience anxiety. Similar parts of the brain are activated when rodents and when humans observe a dangerous situation, the amygdala playing a crucial role in this assessment. By observing the amygdala’s functions, people can determine why one rodent may be much more anxious than another. There is a direct relationship between the activation of the amygdala and the level of anxiety the subject feels.

Feelings of anxiety start with a catalyst – an environmental stimulus that provokes stress. This can include various smells, sights, and internal feelings that result in anxiety. The amygdala reacts to this stimuli by preparing to either stand and fight or to turn and run. This response is triggered by the release of adrenaline into the bloodstream. Consequently, blood sugar rises, becoming immediately available to the muscles for quick energy. Shaking may occur in an attempt to return blood to the rest of the body. A better understanding of the amygdala and its various functions may lead to a new way of treating clinical anxiety.[73]

Posttraumatic stress disorder

There seems to be a connection with the amygdalae and how the brain processes posttraumatic stress disorder. Multiple studies have found that the amygdalae may be responsible for the emotional reactions of PTSD patients. One study in particular found that when PTSD patients are shown pictures of faces with fearful expressions, their amygdalae tended to have a higher activation than someone without PTSD.[74]

Political orientation

Amygdala size has been correlated with cognitive styles with regard to political thinking. A study found that “greater liberalism was associated with increased gray matter volume in the anterior cingulate cortex, whereas greater conservatism was associated with increased volume of the right amygdala.”[75]

The nucleus accumbens

The nucleus accumbens (NAc or NAcc), also known as the accumbens nucleus or as the nucleus accumbens septi (Latin fornucleus adjacent to the septum) is a region in the basal forebrain rostral to the preoptic area of the hypothalamus.[1] The nucleus accumbens and the olfactory tubercle collectively form the ventral striatum, which is part of […]

The nucleus accumbens (NAc or NAcc), also known as the accumbens nucleus or as the nucleus accumbens septi (Latin fornucleus adjacent to the septum) is a region in the basal forebrain rostral to the preoptic area of the hypothalamus.[1] The nucleus accumbens and the olfactory tubercle collectively form the ventral striatum, which is part of the basal ganglia.[2] Each cerebral hemisphere has its own nucleus accumbens, which can be divided into two structures: the nucleus accumbens core and the nucleus accumbens shell. These substructures have different morphology and functions.

Different NAcc subregions (core vs shell) and neuron subpopulations within each region (D1-type vs D2-type medium spiny neurons) are responsible for different cognitive functions.[3][4] As a whole, the nucleus accumbens has a significant role in the cognitive processing of aversion, motivation, pleasure, reward and reinforcement learning;[5][6][7] hence, it has a significant role inaddiction.[6][7] It plays a lesser role in processing fear (a form of aversion), impulsivity, and the placebo effect.[8][9][10] It is involved in the encoding of new motor programs as well.[6]

Major inputs to the nucleus accumbens include the prefrontal cortex, basolateral amygdala, and dopaminergic neurons located in the ventral tegmental area (VTA), which connect via the mesolimbic pathway. Thus the nucleus accumbens is often described as one part of a cortico–basal ganglia–thalamic loop.[11]

Dopaminergic input from the VTA modulate the activity of neurons within the nucleus accumbens. These neurons are activated directly or indirectly by euphoriant drugs (e.g.,amphetamine, opiates, etc.) and by participating in rewarding experiences (e.g., sex, music, exercise, etc.).[12][13]

Another major source of input comes from the CA1 and ventral subiculum of the hippocampus to the dorsomedial area of the nucleus accumbens. The neurons of the hippocampus have a noteworthy correlation to slight depolarizations of cells in the nucleus accumbens, which makes them more positive and therefore more excitable. The correlated cells of these excited states of the medium spiny neurons in the nucleus accumbens are shared equally between the subiculum and CA1. The subiculum neurons are found to hyperpolarize (increase negativity) while the CA1 neurons “ripple” (fire > 50 Hz) in order to accomplish this priming.[14]

The nucleus accumbens is one of the few regions that receive histaminergic projections from the tuberomammillary nucleus (the sole source of histamine neurons in the brain).[15]

Output

The output neurons of the nucleus accumbens send axon projections to the basal ganglia and the ventral analog of the globus pallidus, known as the ventral pallidum (VP). The VP, in turn, projects to the medial dorsal nucleus of the dorsal thalamus, which projects to the prefrontal cortex as well as the striatum. Other efferents from the nucleus accumbens include connections with the tail of the ventral tegmental area,[16] substantia nigra, and the reticular formation of the pons.[1]

Neurotransmitters

Dopamine: Dopamine is related to recreational drugs including amphetamines, cocaine, and morphine, which increase extracellular levels of dopamine in both the NAc shell and the NAc core, but the effect of these increases is more pronounced in the shell. Only amphetamine at high levels increases extracellular levels of dopamine to similar levels in both the shell and the core. All of this points to a ‘functional heterogeneity’ in the nucleus accumbens between the shell region and the core region.[26] Similarly to drug rewards, non-drug rewards also increase levels of extracellular dopamine in the NAc shell, but drug induced DA increase is more resilient to habituation when exposed repeatedly to drug-stimuli, unlike non-drug rewarding stimuli induced dopamine increases, which do succumb to habituation. Recent[when?] studies have shown that the repeated influence of drug-inducing DA projection has an abnormal strengthening effect on stimulus-drug associations and increases the drug-reward stimuli’s resistance to extinction. This may be a contributing factor to addiction. This effect was more pronounced in the NAc shell than in the NAc core.[19][27]

Phenethylamine and tyramine: Phenethylamine and tyramine are trace amine compounds which are synthesized in several types of CNS neurons, including all dopamine neurons.[28] Specifically, these neurotransmitters act within the dopaminergic inputs to the NAcc. These substances regulate the presynaptic release of dopamine through their interactions with VMAT2 and TAAR1, analogous to amphetamine.

Glucocorticoids and dopamine: Glucocorticoid receptors are the only corticosteroid receptors in the nucleus accumbens shell. L-DOPA, steroids, and specifically glucocorticoids are currently known to be the only known endogenous compounds that can induce psychotic problems, so understanding the hormonal control over dopaminergic projections with regards to glucocorticoid receptors could lead to new treatments for psychotic symptoms. A recent study demonstrated that suppression of the glucocorticoid receptors led to a decrease in the release of dopamine, which may lead to future research involving anti-glucocorticoid drugs to potentially relieve psychotic symptoms.[29]

Glucocorticoids (GCs) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor (GR),[1] that is present in almost every vertebrate animal cell. The name glucocorticoid (glucose +cortex + steroid) is composed from its role in regulation of glucose metabolisms synthesis in the adrenal cortex, and its steroidalstructure (see structure to the right). A less common synonym is glucocorticosteroid.

GCs are part of the feedback mechanism in the immune system which reduces certain aspects of immune function, such as reduction of inflammation. They are therefore used in medicine to treat diseases caused by an overactive immune system, such as allergies, asthma, autoimmune diseases, and sepsis. GCs have many diverse (pleiotropic) effects, including potentially harmful side effects, and as a result are rarely sold over the counter.[2] They also interfere with some of the abnormal mechanisms in cancer cells, so they are used in high doses to treat cancer. This includes: inhibitory effects on lymphocyte proliferation as in the treatment of lymphomas and leukemias; and the mitigation of side effects of anticancer drugs.

GCs affect cells by binding to the glucocorticoid receptor (GR). The activated GR complex, in turn, up-regulates the expression of anti-inflammatory proteins in the nucleus (a process known as transactivation) and represses the expression of proinflammatory proteins in the cytosol by preventing the translocation of other transcription factors from the cytosol into the nucleus (transrepression).[2]

Glucocorticoids are distinguished from mineralocorticoids and sex steroids by their specific receptors, target cells, and effects. In technical terms, “corticosteroid” refers to both glucocorticoids and mineralocorticoids (as both are mimics of hormones produced by the adrenal cortex), but is often used as a synonym for “glucocorticoid.” Glucocorticoids are chiefly produced in the zona fasciculataof the adrenal cortex, whereas mineralocorticoids are synthesized in the zona glomerulosa.

Cortisol (or hydrocortisone) is the most important human glucocorticoid. It is essential for life, and it regulates or supports a variety of important cardiovascular, metabolic, immunologic, and homeostatic functions. Various synthetic glucocorticoids are available; these are used either as replacement therapy in glucocorticoid deficiency or to suppress the immune system.

Glucocorticoids act on the hippocampus, amygdala, and frontal lobes. Along with adrenaline, these enhance the formation of flashbulb memories of events associated with strong emotions, both positive and negative.[5] This has been confirmed in studies, whereby blockade of either glucocorticoids or noradrenaline activity impaired the recall of emotionally relevant information. Additional sources have shown subjects whose fear learning was accompanied by high cortisol levels had better consolidation of this memory (this effect was more important in men). The effect that glucocorticoids have on memory may be due to damage specifically to the CA1 area of the hippocampal formation. In multiple animal studies, prolonged stress (causing prolonged increases in glucocorticoid levels) have shown destruction of the neurons in this area of the brain, which has been connected to memory performance.[6][7][8]

Glucocorticoids have also been shown to have a significant impact on vigilance (attention deficit disorder) and cognition (memory). This appears to follow the Yerkes-Dodson curve, as studies have shown circulating levels of glucocorticoids vs. memory performance follow an upside-down U pattern, much like the Yerkes-Dodson curve. For example, long-term potentiation (LTP; the process of forming long-term memories) is optimal when glucocorticoid levels are mildly elevated, whereas significant decreases of LTP are observed after adrenalectomy (low-GC state) or after exogenous glucocorticoid administration (high-GC state). Elevated levels of glucocorticoids enhance memory for emotionally arousing events, but lead more often than not to poor memory for material unrelated to the source of stress/emotional arousal.[9] In contrast to the dose-dependent enhancing effects of glucocorticoids on memory consolidation, these stress hormones have been shown to inhibit the retrieval of already stored information.[10] Long-term exposure to glucocorticoid medications, such as asthma and anti-inflammatory medication, has been shown to create deficits in memory and attention both during and, to a lesser extent, after treatment,[11][12] a condition known as “steroid dementia.”[13]

GABA: A recent study on rats that used GABA agonists and antagonists indicated that GABAA receptors in the NAc shell have inhibitory control on turning behavior influenced by dopamine, and GABAB receptors have inhibitory control over turning behavior mediated by acetylcholine.[19][30]

Glutamate: Studies have shown that local blockade of glutamatergic NMDA receptors in the NAcc core impaired spatial learning.[31] Another study demonstrated that both NMDA and AMPA (both glutamate receptors) play important roles in regulating instrumental learning.[32]

Serotonin (5-HT): Overall, 5-HT synapses are more abundant and have a greater number of synaptic contacts in the NAc shell than in the core. They are also larger and thicker, and contain more large dense core vesicles than their counterparts in the core.

Reward and reinforcement

The nucleus accumbens, being one part of the reward system, plays an important role in processing rewarding stimuli, reinforcing stimuli (e.g., food and water), and those which are both rewarding and reinforcing (addictive drugs, sex, and exercise).[6][33] The nucleus accumbens is selectively activated during the perception of pleasant, emotionally arousing pictures and during mental imagery of pleasant, emotional scenes.[34][35] A 2005 study found that it is involved in the regulation of emotions induced by music,[36]perhaps consequent to its role in mediating dopamine release. The nucleus accumbens plays a role in rhythmic timing and is considered to be of central importance to the limbic-motor interface (Mogensen).[citation needed]

In the 1950s, James Olds and Peter Milner implanted electrodes into the septal area of the rat and found that the rat chose to press a lever which stimulated it. It continued to prefer this even over stopping to eat or drink. This suggests that the area is the “pleasure center” of the brain and is involved in reinforcement learning.[37] In rats, stimulation of the ventral tegmental area causes the release of dopamine in the nucleus accumbens much in the same way as addictive drugs and natural reinforcers, such as water or food, initiate the release of dopamine in the nucleus accumbens.[38] The same results have been seen in human subjects in functional imaging studies. For example, increased dopamine concentration is seen in the extracellular fluid of the nucleus accumbens when subjects believed they were being given money[citation needed], and increased activation (i.e., increased fMRI BOLD signal-change) was observed among heterosexual males viewing pictures of attractive women.[39]

Aversion

Activation of D1-type MSNs in the nucleus accumbens is involved in reward, whereas the activation of D2-type MSNs in the nucleus accumbens promotes aversion.[4]

Maternal behavior

An fMRI study conducted in 2005 found that when mother rats were in the presence of their pups the regions of the brain involved in reinforcement, including the nucleus accumbens, were highly active.[40] Levels of dopamine increase in the nucleus accumbens during maternal behavior, while lesions in this area upset maternal behavior.[41] When women are presented pictures of unrelated infants, fMRIs show increased brain activity in the nucleus accumbens and adjacent caudate nucleus, proportionate to the degree to which the women find these infants “cute”.[42]

Placebo effect

Activation of the NAcc has been shown to occur in the anticipation of effectiveness of a drug when a user is given a placebo, indicating a contributing role of the nucleus accumbens in the placebo effect.[9][52]

Purinergic signalling

Purinergic signalling (or signaling: see American and British English differences) is a form of extracellular signalling mediated bypurine nucleotides and nucleosides such as adenosine and ATP. It involves the activation of purinergic receptors in the cell and/or in nearby cells, thereby regulating cellular functions.[1] The purinergic signalling complex of a cell is sometimes referred to […]

Purinergic signalling (or signaling: see American and British English differences) is a form of extracellular signalling mediated bypurine nucleotides and nucleosides such as adenosine and ATP. It involves the activation of purinergic receptors in the cell and/or in nearby cells, thereby regulating cellular functions.[1]

The purinergic signalling complex of a cell is sometimes referred to as the “purinome”.

Peptides

Peptides (from Gr. πεπτός, “digested”, derived from πέσσειν, “to digest”) are biologically occurring short chains of amino acid monomers linked by peptide (amide) bonds. The covalent chemical bonds are formed when the carboxyl group of one amino acid reacts with the amine group of another. The shortest peptides are dipeptides, consisting of 2 amino acids […]

Peptides (from Gr. ??????, “digested”, derived from ???????, “to digest”) are biologically occurring short chains of amino acid monomers linked by peptide (amide) bonds.

The covalent chemical bonds are formed when the carboxyl group of one amino acid reacts with the amine group of another. The shortest peptides are dipeptides, consisting of 2 amino acids joined by a single peptide bond, followed by tripeptides,tetrapeptides, etc. A polypeptide is a long, continuous, and unbranched peptide chain. Hence, peptides fall under the broad chemical classes of biological oligomers and polymers, alongside nucleic acids, oligosaccharides and polysaccharides, etc.

Peptides are distinguished from proteins on the basis of size, and as an arbitrary benchmark can be understood to contain approximately 50 or fewer amino acids.[1][2] Proteins consist of one or more polypeptides arranged in a biologically functional way, often bound to ligands such as coenzymes and cofactors, or to another protein or other macromolecule (DNA, RNA, etc.), or to complex macromolecular assemblies. Finally, while aspects of the lab techniques applied to peptides versus polypeptides and proteins differ (e.g., the specifics of electrophoresis, chromatography, etc.), the size boundaries that distinguish peptides from polypeptides and proteins are not absolute: long peptides such as amyloid beta have been referred to as proteins, and smaller proteins like insulin have been considered peptides.

Amino acids that have been incorporated into peptides are termed “residues” due to the release of either a hydrogen ion from the amine end or a hydroxyl ion from the carboxyl end, or both, as a water molecule is released during formation of each amide bond.[3] All peptides except cyclic peptides have an N-terminal and C-terminal residue at the end of the peptide (as shown for the tetrapeptide in the image).

Trace amines

Trace amines are an endogenous group of trace amine associated receptor 1 (TAAR1) agonists[1] – and hence, monoaminergic neuromodulators[2][3][4] – that are structurally and metabolically related to classical monoamine neurotransmitters.[5] Compared to the classical monoamines, they are present in trace concentrations.[5] They are distributed heterogeneously throughout the mammalian brain and peripheral nervous tissues and exhibit high […]

Trace amines are an endogenous group of trace amine associated receptor 1 (TAAR1) agonists[1] – and hence, monoaminergic neuromodulators[2][3][4] – that are structurally and metabolically related to classical monoamine neurotransmitters.[5] Compared to the classical monoamines, they are present in trace concentrations.[5] They are distributed heterogeneously throughout the mammalian brain and peripheral nervous tissues and exhibit high rates of metabolism.[5][6] Although they can be synthesized within parent monoamine neurotransmitter systems,[7] there is evidence that suggests that some of them may comprise their own independent neurotransmitter systems.[2]

Trace amines play significant roles in regulating the quantity of monoamine neurotransmitters in the synaptic cleft of monoamine neurons with co-localized TAAR1.[6] They have well-characterized presynaptic amphetamine-like effects on these monoamine neurons via TAAR1 activation;[3][4] specifically, by activating TAAR1 in neurons they promote the release[note 1] and prevent reuptake of monoamine neurotransmitters from the synaptic cleft as well as inhibit postsynaptic neuronal firing.[6][8] Phenethylamine and amphetamine possess analogous pharmacodynamics in human dopamine neurons, as both compounds induce efflux from vesicular monoamine transporter 2 (VMAT2)[7][9] and activate TAAR1 with comparable efficacy.[6] Like dopamine, noradrenaline, andserotonin, the trace amines have been implicated in a vast array of human disorders of affect and cognition, such as ADHD,[3][4]depression[3][4] and schizophrenia,[3][4] among others.[3][4] Trace aminergic hypo-function is particularly relevant to ADHD, since the two most commonly prescribed drugs for ADHD, amphetamine and methylphenidate, increase phenethylamine biosynthesis in treatment-responsive individuals with ADHD.[3][10]

A thorough review of trace amine-associated receptors that discusses the historical evolution of this research particularly well is that of Grandy.[11]

Monoamine neurotransmitters

Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group that is connected to an aromatic ring by a two-carbon chain (-CH2-CH2-). All monoamines are derived from aromatic amino acids like phenylalanine, tyrosine, tryptophan, and thethyroid hormones by the action of aromatic amino acid decarboxylase enzymes. Monoaminergic systems, i.e., the networks of neurons that […]

Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group that is connected to an aromatic ring by a two-carbon chain (-CH2-CH2-). All monoamines are derived from aromatic amino acids like phenylalanine, tyrosine, tryptophan, and thethyroid hormones by the action of aromatic amino acid decarboxylase enzymes. Monoaminergic systems, i.e., the networks of neurons that utilize monoamine neurotransmitters, are involved in the regulation of cognitive processes such as emotion, arousal, and certain types of memory. It has been found that monoamine neurotransmitters play an important role in the secretion and production of neurotrophin-3 by astrocytes, a chemical which maintains neuron integrity and provides neurons with trophic support.[1] Drugs used to increase (or reduce) the effect of monoamine are sometimes used to treat patients with psychiatric disorders, including depression, anxiety, and schizophrenia.[2]

aromaticity

In organic chemistry, the term aromaticity is used to describe a cyclic (ring-shaped), planar (flat) molecule that exhibits unusual stability as compared to other geometric or connective arrangements of the same set of atoms. As a result of their stability, it is very difficult to cause aromatic molecules to break apart and to react with […]

In organic chemistry, the term aromaticity is used to describe a cyclic (ring-shaped), planar (flat) molecule that exhibits unusual stability as compared to other geometric or connective arrangements of the same set of atoms. As a result of their stability, it is very difficult to cause aromatic molecules to break apart and to react with other substances. Organic compounds that are not aromatic are classified asaliphatic compounds—they might be cyclic, but only aromatic rings have especial stability (low reactivity).

Since one of the most commonly encountered aromatic systems of compounds in organic chemistry is based on derivatives of the prototypical aromatic compound benzene (an aromatic hydrocarbon common in petroleum and its distillates), the word “aromatic” is occasionally used to refer informally to benzene derivatives, and this is how it was first defined. Nevertheless, many non-benzene aromatic compounds exist. In living organisms, for example, the most common aromatic rings are the double-ringed bases in RNA andDNA. A functional group or other substituent that is aromatic is called an aryl group.

The earliest use of the term “aromatic” was in an article by August Wilhelm Hofmann in 1855.[1] Hofmann used the term for a class of benzene compounds, many of which do have odors (aromas), unlike pure saturated hydrocarbons. Today, there is no general relationship between aromaticity as a chemical property and the olfactory properties of such compounds (how they smell), although in 1855, before the structure of benzene or organic compounds was understood, chemists like Hofmann were beginning to understand that odiferous molecules from plants, such as terpenes, had chemical properties we recognize today are similar to unsaturated petroleum hydrocarbons like benzene.

In terms of the electronic nature of the molecule, aromaticity describes a conjugated system often made of alternating single and double bonds in a ring. This configuration allows for the electrons in the molecule’s pi system to be delocalized around the ring, increasing the molecule’s stability. The molecule cannot be represented by one structure, but rather a resonance hybrid of different structures, such as with the two resonance structures of benzene.

Gaseous signaling molecules

Gaseous signaling molecules are gaseous molecules that are either synthesised internally (endogenously) in the organism, tissue or cell or are received by the organism, tissue or cell from outside (say, from the atmosphere or hydrosphere, as in the case of oxygen) and that are used to transmit chemical signals which induce certain physiological or biochemical […]

Gaseous signaling molecules are gaseous molecules that are either synthesised internally (endogenously) in the organism, tissue or cell or are received by the organism, tissue or cell from outside (say, from the atmosphere or hydrosphere, as in the case of oxygen) and that are used to transmit chemical signals which induce certain physiological or biochemical changes in the organism, tissue or cell. The term is applied to, for example, oxygen, carbon dioxide, nitric oxide, carbon monoxide, hydrogen sulfide, sulfur dioxide, nitrous oxide, hydrogen cyanide, ammonia, methane, hydrogen, ethylene etc.

Many, but not all, gaseous signaling molecules are called gasotransmitters.

Gasotransmitters is a subfamily of endogenous molecules of gases or gaseous signaling molecules, including NO, CO, H2S.[1] These particular gases share many common features in their production and function but carry on their tasks in unique ways, which differ from classical signaling molecules, in the human body. The first suggestion that a gas had a direct action at pharmacological receptors and thereby acting as a neurotransmitter was first suggested in 1981 from clinical work with nitrous oxide.[2][3][4] In vitro experiments confirmed these observations[5] which were replicated at NIDA later.[6]

The terminology and characterization criteria of “gasotransmitter” were firstly introduced in 2002.[7] For one gas molecule to be categorized as a gasotransmitters, all of the following criteria should be met.[8][7]

  1. It is a small molecule of gas;
  2. It is freely permeable to membranes. As such, its effects do not rely on the cognate membrane receptors. It can have endocrine, paracrine, and autocrine effects. In their endocrine mode of action, for example, gasotransmitters can enter the blood stream; be carried to remote targets by scavengers and released there, and modulate functions of remote target cells;
  3. It is endogenously and enzymatically generated and its production is regulated;
  4. It has well defined and specific functions at physiologically relevant concentrations. Thus, manipulating the endogenous levels of this gas evokes specific physiological changes;
  5. Functions of this endogenous gas can be mimicked by its exogenously applied counterpart;
  6. Its cellular effects may or may not be mediated by second messengers, but should have specific cellular and molecular targets.

In 2011, a European Network on Gasotransmitters (ENOG) was formed. The aim of the network is to promote research on NO, CO and H2S in order to better understand the biology of gasotransmitters and to unravel the role of each mediator in health and disease. Moreover, the network aims to contribute to the translation of basic science knowledge in this area of research into therapeutic or diagnostic tools.

Amino acids

Amino acids are biologically important organic compounds containing amine (-NH2) and carboxylic acid (-COOH) functional groups, usually along with a side-chain specific to each amino acid.[1][2][3] The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen, though other elements are found in the side-chains of certain amino acids. About 500 amino acids […]

Amino acids are biologically important organic compounds containing amine (-NH2) and carboxylic acid (-COOH) functional groups, usually along with a side-chain specific to each amino acid.[1][2][3] The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen, though other elements are found in the side-chains of certain amino acids. About 500 amino acids are known and can be classified in many ways.[4] They can be classified according to the core structural functional groups’ locations as alpha- (?-), beta- (?-), gamma- (?-) or delta-(?-) amino acids; other categories relate to polarity, pH level, and side-chain group type (aliphatic, acyclic, aromatic, containing hydroxyl orsulfur, etc.). In the form of proteins, amino acids comprise the second-largest component (water is the largest) of human muscles, cells and other tissues.[5] Outside proteins, amino acids perform critical roles in processes such as neurotransmitter transport and biosynthesis.

In biochemistry, amino acids having both the amine and the carboxylic acid groups attached to the first (alpha-) carbon atom have particular importance. They are known as 2-, alpha-, or ?-amino acids (generic formula H2NCHRCOOH in most cases,[6] where R is an organicsubstituent known as a “side-chain“);[7] often the term “amino acid” is used to refer specifically to these. They include the 23 proteinogenic (“protein-building”) amino acids,[8][9][10] which combine into peptidechains (“polypeptides”) to form the building-blocks of a vast array of proteins.[11] These are all Lstereoisomers (“left-handedisomers), although a few D-amino acids (“right-handed”) occur in bacterial envelopes, as a neuromodulator (D-serine), and in some antibiotics.[12] Twenty of the proteinogenic amino acids are encoded directly by triplet codons in the genetic code and are known as “standard” amino acids. The other three (“non-standard” or “non-canonical”) are selenocysteine (present in many noneukaryotes as well as most eukaryotes, but not coded directly by DNA), pyrrolysine (found only in some archea and one bacterium) and N-formylmethionine (which is often the initial amino acid of proteins in bacteria, mitochondria, and chloroplasts). Pyrrolysine and selenocysteine are encoded via variant codons; for example, selenocysteine is encoded by stop codon and SECIS element.[13][14][15]Codon–tRNA combinations not found in nature can also be used to “expand” the genetic code and create novel proteins known as alloproteins incorporating non-proteinogenic amino acids.[16][17][18]

Many important proteinogenic and non-proteinogenic amino acids also play critical non-protein roles within the body. For example, in the human brain, glutamate (standard glutamic acid) and gamma-amino-butyric acid (“GABA”, non-standard gamma-amino acid) are, respectively, the main excitatory and inhibitory neurotransmitters;[19] hydroxyproline (a major component of the connective tissuecollagen) is synthesised from proline; the standard amino acid glycine is used to synthesise porphyrins used in red blood cells; and the non-standard carnitine is used in lipid transport.

Nine proteinogenic amino acids are called “essential” for humans because they cannot be created from other compounds by the human body and so must be taken in as food. Others may be conditionally essential for certain ages or medical conditions. Essential amino acids may also differ betweenspecies.[20]

Because of their biological significance, amino acids are important in nutrition and are commonly used in nutritional supplements, fertilizers, and food technology. Industrial uses include the production ofdrugs, biodegradable plastics, and chiral catalysts.