Shell Part Of Nucleus Accumbens Research Articles

Characterization of orexin input to dopamine neurons of the ventral tegmental area projecting to the medial prefrontal cortex and shell of nucleus accumbens

Orexin neurons are involved in homeostatic regulatory processes, including arousal and feeding, and provide a major input from the hypothalamus to the ventral tegmental area (VTA) of the midbrain. VTA neurons are a central hub processing reward and motivation and target the medial prefrontal cortex (mPFC) and the shell part of nucleus accumbens (NAcs). We investigated whether subpopulations of dopamine (DA) neurons in the VTA projecting either to the mPFC or the medial division of shell part of nucleus accumbens (mNAcs) receive differential input from orexin neurons and whether orexin exerts differential electrophysiological effects upon these cells. VTA neurons projecting to the mPFC or the mNAcs were traced retrogradely by Cav2-Cre virus and identified by expression of yellow fluorescent protein (YFP). Immunocytochemical analysis showed that a higher proportion of all orexin-innervated DA neurons projected to the mNAcs (34.5%) than to the mPFC (5.2%). Of all sampled VTA neurons projecting either to the mPFC or mNAcs, the dopaminergic (68.3 vs. 79.6%) and orexin-innervated DA neurons (68.9 vs. 64.4%) represented the major phenotype. Whole-cell current clamp recordings were obtained from fluorescently labeled neurons in slices during baseline periods and bath application of orexin A. Orexin similarly increased the firing rate of VTA dopamine neurons projecting to mNAcs (1.99 ± 0.61 Hz to 2.53 ± 0.72 Hz) and mPFC (0.40 ± 0.22 Hz to 1.45 ± 0.56 Hz). Thus, the hypothalamic orexin system targets mNAcs and to a lesser extent mPFC-projecting dopaminergic neurons of the VTA and exerts facilitatory effects on both clusters of dopamine neurons.

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

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.

Transient Inactivation of Shell Part of Nucleus Accumbens Inhibits and Exacerbates Stress-Induced Metabolic Alterations in Wistar Rats.

Introduction:The role of different parts of the extended amygdala in metabolic signs of stress is not well understood. In the present study, we decided to evaluate the impact of the shell part of nucleus accumbens (NAc) on metabolic disturbance induced by electro foot shock stress using transient inactivation method in the rat.Methods:Male Wistar rats (W: 230–250 g) were canuulated unilaterally in the shell part of nucleus accumbens and left one week for recovery. Five minutes before each stress session, the animals either received sterile saline (0.25 μl/side) (control) or lidocaine 2% (0.25 μl/side) (experiment). Blood samples were taken from rats’ retro-orbital sinus for plasma corticosterone measurements. In addition, animals’ weight gain, food and water intake, locomotor activity, and rearing were recorded.Results:Stress reduced weight gain and food intake, increased water intake and plasma corticosterone level, and reduces locomotor activity and rearing. Transient inactivation of the right side of the NAc inhibits the stress effect on weight gain, water intake and plasma corticosterone level, but not food intake. However, when the left side of the NAc was inactivated, only weight gain was affected and other parameters were not differing from stress group. Even thought, the plasma corticosterone level was elevated.Conclusion:In conclusion, our data indicated that right side of shell part of NAc transient inactivation leads to reduction in metabolic signs of stress but left side of shell part of the NAc inactivation even exacerbates stress signs.

Neurotoxicity of Synthetic Cannabinoids JWH-081 and JWH-210

Synthetic cannabinoids JWH-018 and JWH-250 in ‘herbal incense’ also called ‘spice’ were first introduced in many countries. Numerous synthetic cannabinoids with similar chemical structures emerged simultaneously and suddenly. Currently there are not sufficient data on their adverse effects including neurotoxicity. There are only anecdotal reports that suggest their toxicity. In the present study, we evaluated the neurotoxicity of two synthetic cannabinoids (JWH-081 and JWH-210) through observation of various behavioral changes and analysis of histopathological changes using experimental mice with various doses (0.1, 1, 5 mg/kg). In functional observation battery (FOB) test, animals treated with 5 mg/kg of JWH-081 or JWH-210 showed traction and tremor. Their locomotor activities and rotarod retention time were significantly (p<0.05) decreased. However, no significant change was observed in learning or memory function. In histopathological analysis, neural cells of the animals treated with the high dose (5 mg/kg) of JWH-081 or JWH-210 showed distorted nuclei and nucleus membranes in the core shell of nucleus accumbens, suggesting neurotoxicity. Our results suggest that JWH-081 and JWH-210 may be neurotoxic substances through changing neuronal cell damages, especially in the core shell part of nucleus accumbens. To confirm our findings, further studies are needed in the future.

Transient inactivation of the nucleus accumbens reduces both the expression and acquisition of morphine-induced conditioned place preference in rats

In the present study, the effects of transient inhibition of the shell and core parts of the nucleus accumbens by lidocaine on the expression and acquisition of morphine-induced conditioned place preference in male Wistar rats were investigated. In addition, the number of bouts of sniffing, rearing, and compartment crossing was scored. Lidocaine hydrochloride was injected into different parts of the nucleus accumbens 5min before each morphine session for the transient inhibition of particular anatomical regions. Subcutaneous (s.c.) injection of morphine (2.5 and 5mg/kg) induced place preference. Transient inhibition of the left and/or right side of the shell part of nucleus accumbens reduced morphine place conditioning. However, when both sides of the nucleus were inhibited, inhibition was weaker when compared to the results when only one side was inhibited. Also, the number of compartment crossings in these animals reduced significantly. Nevertheless, the number of rearing occurrences was reduced only when both sides of the shell part of the nucleus accumbens were inhibited. In contrast, the number of sniffing bouts increased in all three groups. The results for the core part of the nucleus accumbens also indicated that place preference was inhibited after transient inhibition of the left, right, and both sides. However, although the number of total compartment crossings was reduced in all experimental groups, the reduction was not statistically significant. The data obtained was similar to the number of rearings, yet the number of sniffing bouts increased in the experimental groups compared to the control. In conclusion, these results confirmed the involvement of the left and right sides and core and shell parts of the nucleus accumbens in morphine place conditioning.

Antagonism of adenosine A 2A receptors underlies the behavioural activating effect of caffeine and is associated with reduced expression of messenger RNA for NGFI-A and NGFI-B in caudate–putamen and nucleus accumbens

Caffeine, the most widely consumed of all psychostimulant drugs, exerts its action by antagonizing adenosine receptors. To study the arousing properties of caffeine, we injected rats intraperitoneally with vehicle, caffeine (7.5, 15 or 30 mg/kg), the selective adenosine A 2A receptor antagonist, SCH 58261 (3.75 mg/kg) or the selective adenosine A 1 receptor selective antagonist DPCPX (7.5 mg/kg). In a behavioural test it was found that administration of caffeine and SCH 58261 significantly increased locomotion and rearing, whereas DPCPX did not alter locomotion and reduced rearing. After the behavioural session the rats were killed, their brains were cut at several levels along a rostrocaudal axis and in situ hybridization against NGFI-A messenger RNA and NGFI-B messenger RNA was performed. A reduction of NGFI-A messenger RNA was found in several subregions of both caudate–putamen and nucleus accumbens in caffeine-treated animals. Similarly, animals that had received SCH 58261 showed significant decreases of NGFI-A messenger RNA in the rostral part of caudate–putamen and in the shell part of nucleus accumbens. By contrast, DPCPX treatment caused an increase in the expression of NGFI-A messenger RNA and a smaller increase in NGFI-B messenger RNA in the lateral parts of caudate–putamen. In addition, it was found that caffeine, but not SCH 58261 or DPCPX, elevated the expression of NGFI-A and NGFI-B messenger RNA in the cerebral cortex, especially in its parietal part. Thus, these results provide evidence that endogenous adenosine, via adenosine A 2A receptors, causes a tonic activation of striatopallidal neurons. By blocking this adenosine effect, caffeine causes behavioural activation.