Pharmacological enhancement of the endocannabinoid system in the nucleus accumbens shell stimulates food intake and increases c-Fos expression in the hypothalamus

AbstractMelanin-concentrating hormone (MCH) is an orexigenic neuropeptide produced in the lateral hypothalamus and zona incerta that increases food intake. The neuronal pathways and behavioral mechanisms mediating the orexigenic effects of MCH are poorly understood, as is the extent to which MCH-mediated feeding outcomes are sex-dependent. Here we investigate the hypothesis that MCH-producing neurons act in the nucleus accumbens shell (ACBsh) to promote feeding behavior and motivation for palatable food in a sex-dependent manner. We utilized ACBsh MCH receptor (MCH1R)-directed pharmacology as well as a dual virus chemogenetic approach to selectively activate MCH neurons that project to the ACBsh. Results reveal that both ACBsh MCH1R activation and activating ACBsh-projecting MCH neurons increase consumption of standard chow and palatable sucrose in male rats without affecting motivated operant responding for sucrose, general activity levels, or anxiety-like behavior. In contrast, food intake was not affected in female rats by either ACBsh MCH1R activation or ACBsh-projecting MCH neuron activation. To determine a mechanism for this sexual dimorphism, we investigated whether the orexigenic effect of ACBsh MCH1R activation is reduced by endogenous estradiol signaling. In ovariectomized female rats on a cyclic regimen of either estradiol (EB) or oil vehicle, ACBsh MCH1R activation increased feeding only in oil-treated rats, suggesting that EB attenuates the ability of ACBsh MCH signaling to promote food intake. Collective results show that that MCH ACBsh signaling promotes feeding in an estrogen- and sex-dependent manner, thus identifying novel neurobiological mechanisms through which MCH and female sex hormones interact to influence food intake.

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Differential effects of central or intra nucleus accumbens shell MCHR1 signalling on food intake and energy expenditure, assessed by indirect calorimetry

Appetite ◽

10.1016/j.appet.2008.04.100 ◽

2008 ◽

Vol 51 (2) ◽

pp. 369

Author(s):

B. Guesdon ◽

P. Samson ◽

D. Richard

Keyword(s):

Nucleus Accumbens ◽

Food Intake ◽

Energy Expenditure ◽

Indirect Calorimetry ◽

Nucleus Accumbens Shell ◽

Differential Effects

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Control of food intake by MC4-R signaling in the lateral hypothalamus, nucleus accumbens shell and ventral tegmental area: Interactions with ethanol

Behavioural Brain Research ◽

10.1016/j.bbr.2012.06.006 ◽

2012 ◽

Vol 234 (1) ◽

pp. 51-60 ◽

Cited By ~ 20

Author(s):

Jose M. Lerma-Cabrera ◽

Francisca Carvajal ◽

Lourdes de la Torre ◽

Leticia de la Fuente ◽

Montserrat Navarro ◽

...

Keyword(s):

Nucleus Accumbens ◽

Food Intake ◽

Ventral Tegmental Area ◽

Lateral Hypothalamus ◽

Nucleus Accumbens Shell ◽

Ventral Tegmental

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The galanin receptor-3 antagonist, SNAP 37889, inhibits cue-induced reinstatement of alcohol-seeking and increases c-Fos expression in the nucleus accumbens shell of alcohol-preferring rats

Journal of Psychopharmacology ◽

10.1177/0269881118780015 ◽

2018 ◽

Vol 32 (8) ◽

pp. 911-921 ◽

Cited By ~ 2

Author(s):

Kira-Elise Wilson ◽

Sigrid Limburg ◽

Melissa K Duggan ◽

Adam J Lawther ◽

Spencer J Williams ◽

...

Keyword(s):

Prefrontal Cortex ◽

Nucleus Accumbens ◽

Medial Prefrontal Cortex ◽

Dopamine Neurons ◽

Nucleus Accumbens Shell ◽

Nucleus Accumbens Core ◽

Fos Protein ◽

Fos Expression ◽

Dual Label ◽

Alcohol Seeking

Introduction: This study aimed to investigate the effects of the galanin-3 receptor antagonist, SNAP 37889, on c-Fos protein expression after cue-induced reinstatement of alcohol-seeking in the brains of alcohol-preferring rats. Methods: Eighteen alcohol-preferring rats were trained to self-administer 10% v/v ethanol in the presence of response-contingent cues, which was followed by extinction. Rats were then treated with SNAP 37889 (30 mg/kg, i.p.) or vehicle, before being tested for cue-induced reinstatement. Administration of SNAP 37889 reduced cue-induced reinstatement of ethanol-seeking behaviour. To examine the effect of SNAP 37889 and cue-induced reinstatement on neuronal activation, c-Fos expression was measured in subregions of the medial prefrontal cortex and nucleus accumbens. Results: SNAP 37889 administration increased c-Fos immunoreactivity in the nucleus accumbens shell, but was without effect in the nucleus accumbens core and the medial prefrontal cortex. Dual-label Fos/tyrosine hydroxylase immunohistochemistry was used to examine the effects of SNAP 37889 on dopamine neurons in the ventral tegmental area; however, no differences between SNAP 37889 and vehicle-treated rats were found. Conclusions: These data support previous findings of galanin-3 receptor involvement in cue-induced reinstatement of alcohol-seeking behaviour, and provide novel evidence that the ability of galanin-3 receptor antagonism to attenuate cue-induced reinstatement relates to activation of the nucleus accumbens shell.

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