SHELL Part of Nucleus Accumbens and Its Laterality Has Important Role in Response to Chronic Stress in Female Rats

Abstract The nucleus accumbens shell (NAcSh) plays a role in appetitive and negative motivation with sex differences in responses. NAcSh and its laterality in metabolic and hormonal responses to chronic stress in female rats is evaluated via transient inactivation of this nucleus during stress induction. Animals in the stress groups received consecutive stress for four days and transient inactivation of NAcSh was performed by administrating lidocaine (0.2%) unilaterally or bilaterally in the nucleus for five minutes before electric foot shock induction. After stress termination, food and water intake, latency to eat, plasma glucose, corticosterone, estradiol and progesterone were measured in all groups. Results showed that stress increased food intake and blood glucose level, but there were no change in the latency to eat and the amount of water intake. The right side, the left side, and both sides of NAcSh may be dominant in latency to eat, food intake, and both water intake and plasma glucose level, respectively. Although chronic stress included no changes for corticosterone and progesterone, it increased estradiol level in plasma. Also, bilateral and right sides of NAcSh may have modulatory effects on stress in corticosterone and progesterone, respectively, without affecting estradiol. It can be concluded that the NAc shell plays a pivotal role in metabolic and hormonal responses to chronic stress in a laterality manner in female rats.

El circuito cerebral de la recompensa en los trastornos afectivos / Brain Reward Circuitry in Affective Disorders

Los síntomas conductuales de la depresión son numerosos y variados, cubriendo los dominios emocionales, motivacionales, cognitivos y fisiológicos. Estudios recientes en modelos animales de depresión y en pacientes depresivos utilizando técnicas neuropsicológicas combinadas con imagenología funcional muestran que grandes subgrupos de estos pacientes presentan deficiencias en el procesamiento de las recompensas a los estímulos emocionales positivos, que son nucleares en depresión. La proteína Rac 1, un regulador crítico de la actina del citoesqueleto, se reduce en el NAcc tanto en depresión como en modelos animales de adicción, lo que lleva al crecimiento de espinas dendríticas inmaduras en las MSNs del NAcc y esto es consecuencia de modificaciones epigenéticas selectivas en esta región, del gen que codifica Rac 1, tanto en modelos de estrés en roedores como en humanos depresivos (estudios post-mortem). El gran desarrollo de algunos de los modelos experimentales de depresión que cuentan con evidencias moleculares, sistémicas y conductuales no se han traducido en nuevos medicamentos pero al avanzar en la comprensión patofisiológica del trastorno y sus correlatos neuroimagenológicos, permitirán, junto a las modernas técnicas de investigación, buscar marcadores biológicos de los endofenotipos diferentes que se combinan para generar un trastorno que posee múltiples subtipos que los agrupan en clusters diferentes

The behavioral symptoms of depression are numerous and varied, and encompass the emotional, motivational and physiologic domains. Recent studies in animal models of depression and depressive patients, which used neuropsychological techniques combined with functional imaging, show that large subgroups of these patients display deficiencies in the processing of rewards to positive emotional stimuli, which are nuclear in depression. Rac 1 protein, a critical regulator of cytoskeleton actin, is reduced in the NAcc, both in depression as well as in animal models of addiction, which leads to the growth of immature dendritic spines in the MSNs of the NAcc, and this is the result of selective epigenetic alterations in this region, of the gene that codifies Rac1, both in models of stress in rodents as well as in depressive human beings (post-mortem studies). The great development of some of the experimental models of depression that provide molecular, systemic and behavioral evidences have not translated into new medications, but the progressive pathophysiological understanding of the disorder and its neuroimaging correlates will enable, together with the modern investigations techniques, to search for biological markers of the different endophenotypes that combine to generate a disorder which has multiple subtypes that gather in different clusters

Núcleo accumbens y el sistema motivacional a cargo del apego / Nucleus accumbens and the motivational system of attachment

The concept of attachment involves the pursuit of proximity of both a figure linked, as a partner. For that to happen there must be a motivational system for innate social interaction in all mammals including humans. This motivational system has its seat on the dopaminergic mesocorticolimbic pathway, known as the reward pathway and is where the Nucleus Accumbens plays a key role. This pathway would be selected and highly conserved by evolution as a mechanism for perpetuating genetics. There is a great influence of prosocial neuropeptides Oxitocin (OT) and Vasopressin (ADH) in this way. These are released into socio-sexual experiences, which can be demonstrated in the paradigms of adult-adult attachment (pair bonding) and mother and child attachment. The path of motivation cast into critical periods of development, leaving it vulnerable to what happens in the environment and its damage or disease, henee, would leave traces more or less stable throughout the Ufe eyele of the individual. This could be a initial factor to psychopathology from "attachment disorder" to "addiction" to drugs. The motivation could also be useful as a endophenotype.

El concepto de apego implica la búsqueda de proximidad tanto de una figura vincular, como de un compañero (partner). Para que ocurra debe existir un sistema motivacional por la interacción social innato en todos los mamíferos incluyendo al humano. Este sistema motivacional tiene su asiento neurobiológico en la vía dopaminérgica mesocorticolímbica, denominada de la recompensa y es donde el Núcleo Accumbens juega un rol clave. Esta vía estaría seleccionada y altamente conservada por la evolución como mecanismo para la perpetuación genética. Existe una gran influencia de los neuropéptidos prosociales Oxitocina (OT) y Vasopresina (ADH) en esta vía. Estos se liberan en experiencias socio-sexuales, hecho que se puede demostrar en los paradigmas de apego adulto- adulto (pair bonding) y apego materno-infantil. La vía de la motivación se moldea en períodos críticos del desarrollo, dejándolo vulnerable a lo que suceda en el ambiente y su daño o enfermedad, por lo tanto, dejaría huellas más o menos estables a lo largo del ciclo vital del individuo. Esto podría ser un factor inicial de psicopatología desde trastornos del vínculo hasta la adicción a drogas de abuso. La motivación también podría ser útil como un endofenotipo.

Alteration of ingestive behaviours by nucleus accumbens in normal and streptozotocin-induced diabetic rats.

Twenty-four hour basal food and water intakes were recorded in Wistar rats. Diabetes was produced in a group of rats by injecting streptozotocin (STZ, 75 mg/kg, b.w., IP) and their post-diabetic basal food and water intakes were recorded. Noradrenaline (2 microg) and dopamine (2 microg) were injected separately into the nucleus accumbens through the implanted cannula in non-diabetic and diabetic animals and their 24 hr food and water intakes were recorded. Food and water intakes were also recorded following bilateral electrolytic lesions of nucleus accumbens in both the groups of rats. In diabetic rats, basal food and water intakes were significantly increased in comparison to basal intakes of non-diabetic rats. Following injection of noradrenaline, a significant increase in water intake but not food intake was seen in non-diabetic rats, whereas food and water intakes remained unchanged in diabetic rats. Following injection of dopamine, a significant increase in food and water intakes was observed in non-diabetic rats, whereas dopamine-induced increase in food intake was absent in diabetic rats. The bilateral lesions of nucleus accumbens resulted in a significant inhibition of food and water intakes in non-diabetic rats, whereas inhibition of water intake without change in food intake observed in diabetic rats. However, no difference was observed in the pattern of change in water intake following lesions or dopamine injections between non-diabetic and diabetic rats, whereas difference was observed for food intake. The results suggest that nucleus accumbens activity changes for food intake, but not for water intake in diabetes.

Alteration of preference of food substances in terms of taste & nutritional value following the lesion of two subdistricts of nucleus accumbens.

Adult albino rats of Wistar strain (200 to 250 g) were lesioned at the nucleus accumbens (Acb) either in the shell area (Acbsh) or in the core area (Acbc). The rats were offered a choice of water and 0.2 per cent saccharine or water and 12 per cent sucrose solution. During the prelesion period, the rats preferred water to the sweet tasting fluids. The Acbc lesion shifted the preference to saccharine from water, but rats with the same lesion consumed equal quantities of sucrose and water. On the other hand, lesion of the Acbsh increased the water intake when paired with either sucrose or saccharine. Food intake was also increased in this lesioned group. The results suggest that the Acbc area appears to participate in the mediation of taste of food while the Acbsh area probably regulates feeding behaviour based on the nutritional value of food substances.

Regulatory role of nucleus accumbens in the ingestion of sucrose and saccharine.

Adult albino rats of Wistar strain of 200 to 250 g body weight were lesioned at nucleus accumbens either in the shell area or in core area. The rats were offered 0.2% saccharine solution or 12% sucrose solution or water for drinking. During the prelesion period, rats consumed more of saccharine followed by sucrose and water. The lesion of core area increased the consumption of both the sweet taste solutions but did not affect the water intake. Lesioning of shell area caused an increase in water and sucrose intake whereas saccharine intake remained unaffected. The results suggest that the core area of nucleus accumbens subserves taste induced ingestion and the shell area mediates the effect of nutritional value of food.

Nucleus accumbens lesion does not affect schedule induced polydipsia.

Rats with lesion of nucleus accumbens were hypodipsic under free-feeding conditions. In schedule-induced polydipsia (SIP) tests conducted by reducing the rats to 70% of free-feeding body weight and delivering 60 mg bengal gram pellets on a fixed time 1-min schedule, nucleus accumbens lesions did not delay the acquisition or show a decrease in the maintenance of S.I.P.

Effect of lesions of areas of brain--stimulation reward of one region of brain on operant behaviour for receiving electrical stimulation into sites of another region and on operant behaviour for food reward.

It was aimed to study the effects of lesions of a self-stimulation (SS) area of one region of brain on the SS of another region, and on feeding behaviour in adult Wistar rats (males). The two regions proposed for study were the lateral hypothalamus (LH) and the substantia nigra-ventral tegmental area (SN-VTA). The objective was to elucidate whether each region had its own neural organization for SS behaviour or not, and whether the neural substrates of SS behaviour and feeding behaviour were one, or separate. Four bipolar electrodes were implanted bilaterally in LH and SN-VTA in each rat, and their SS pedal press rates for rewarding electrical stimulations were characterised. The rats were also trained in operant conditioning paradigm for receiving reward of food grains in FR-30 schedule. Their free-field food intake in home cages was measured. Later, electrolytic lesions of the four electrode sites were made one after another at 2-day intervals through the same biopolar electrodes. After each lesioning, the SS of the same and of the other electrode sites, and the operant performance of FR-30 food reward schedule, and daily free-field food intake (in home cage) were determined. Lesions of the LH SS site always disrupted SS-of contralateral LH but not of SN-VTA SS. Lesions of SN-VTA had not modified contralateral SN-VTA SS. A study of effects of ipsilateral lesions of LH SS site on SN-VTA SS, or of lesions of SN-VTA SS site on LH SS, revealed a range of changes, as were also effects on the FR-30 operant performance and daily food intake. Medium size lesions of SS area made in one region affected the SS of that area but not usually the SS of the other region. Large lesions of one region affected the SS of the other regions also. With large lesions, feeding behaviour also was affected, firstly of the operant type and secondly the free-field type.