Ipsilateral feeding-specific circuits between the nucleus accumbens shell and the lateral hypothalamus: Regulation by glutamate and GABA receptor subtypes

Background: Identifying neural substrates that are differentially affected by drugs of abuse and natural rewards is key to finding a target for an efficacious treatment for substance abuse. Melanin-concentrating hormone is a polypeptide with an inhibitory effect on the mesolimbic dopamine system. Here we test the hypothesis that melanin-concentrating hormone in the lateral hypothalamus and nucleus accumbens shell is differentially involved in the regulation of morphine and food-rewarded behaviors. Methods: Male Sprague–Dawley rats were trained with morphine (5.0 mg/kg, subcutaneously) or food pellets (standard chow, 10–14 g) to induce a conditioned place preference, immediately followed by extinction training. Melanin-concentrating hormone (1.0 µg/side) or saline was infused into the nucleus accumbens shell or lateral hypothalamus before the reinstatement primed by morphine or food, and locomotor activity was simultaneously monitored. As the comparison, melanin-concentrating hormone was also microinjected into the nucleus accumbens shell or lateral hypothalamus before the expression of food or morphine-induced conditioned place preference. Results: Microinfusion of melanin-concentrating hormone into the nucleus accumbens shell (but not into the lateral hypothalamus) prevented the reinstatement of morphine conditioned place preference but had no effect on the reinstatement of food conditioned place preference. In contrast, microinfusion of melanin-concentrating hormone into the lateral hypothalamus (but not in the nucleus accumbens shell) inhibited the reinstatement of food conditioned place preference but had no effect on the reinstatement of morphine conditioned place preference. Conclusions: These results suggest a clear double dissociation of melanin-concentrating hormone in morphine/food rewarding behaviors and melanin-concentrating hormone in the nucleus accumbens shell. Melanin-concentrating hormone could be a potential target for therapeutic intervention for morphine abuse without affecting natural rewards.

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GABA receptor subtype antagonists in the nucleus accumbens shell and ventral tegmental area differentially alter feeding responses induced by deprivation, glucoprivation and lipoprivation in rats

Brain Research ◽

10.1016/j.brainres.2006.01.112 ◽

2006 ◽

Vol 1082 (1) ◽

pp. 86-97 ◽

Cited By ~ 11

Author(s):

Y. Kandov ◽

Y. Israel ◽

A. Kest ◽

I. Dostova ◽

J. Verasammy ◽

...

Keyword(s):

Nucleus Accumbens ◽

Ventral Tegmental Area ◽

Gaba Receptor ◽

Receptor Subtype ◽

Nucleus Accumbens Shell ◽

Ventral Tegmental

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Orexin signaling in rostral lateral hypothalamus and nucleus accumbens shell in the control of spontaneous physical activity in high- and low-activity rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00339.2016 ◽

2017 ◽

Vol 312 (3) ◽

pp. R338-R346 ◽

Cited By ~ 13

Author(s):

Claudio Perez-Leighton ◽

Morgan R. Little ◽

Martha Grace ◽

Charles Billington ◽

Catherine M. Kotz

Keyword(s):

Physical Activity ◽

Nucleus Accumbens ◽

Lateral Hypothalamus ◽

Receptor Expression ◽

Nucleus Accumbens Shell ◽

Orexin A ◽

Orexin Neuron ◽

Spontaneous Physical Activity ◽

Low Activity ◽

Higher Sensitivity

Spontaneous physical activity (SPA) describes activity outside of formal exercise and shows large interindividual variability. The hypothalamic orexin/hypocretin peptides are key regulators of SPA. Orexins drive SPA within multiple brain sites, including rostral lateral hypothalamus (LH) and nucleus accumbens shell (NAcSh). Rats with high basal SPA (high activity, HA) show higher orexin mRNA expression and SPA after injection of orexin-A in rostral LH compared with low-activity (LA) rats. Here, we explored the contribution of orexin signaling in rostral LH and NAcSh to the HA/LA phenotype. We found that HA rats have higher sensitivity to SPA after injection of orexin-A in rostral LH, but not in NAcSh. HA and LA rats showed similar levels of orexin receptor expression in rostral LH, and activation of orexin-producing neurons after orexin-A injection in rostral LH. Also, in HA and LA rats, the coinjection of orexin-A in rostral LH and NAcSh failed to further increase SPA beyond the effects of orexin-A in rostral LH. Pretreatment with muscimol, a GABAA receptor agonist, in NAcSh potentiated SPA produced by orexin-A injection in rostral LH in HA but not in LA rats. Our results suggest that a feedback loop from orexin-responsive neurons in rostral LH to orexin neurons and a the NAcSh–orexin neuron–rostral LH circuit regulate SPA. Overall, our data suggest that differences in orexin sensitivity in rostral LH and its modulation by GABA afferents from NAcSh contribute to individual SPA differences.

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