Catestatin and GABAAR related feeding habits rely on dopamine, ghrelin plus leptin neuroreceptor expression variations

Abstract

Catestatin (CST), an endogenously small sympathoinhibitory peptide is capable of interfering with the major cerebral neuroreceptor-blocking site, i.e. γ-aminobutyric acidA receptor (GABAAR) system especially in limbic brain areas that are involved with feeding behaviors. The GABAARergic-related effects seem to derive from its interaction with other molecular neuroreceptors such as dopaminergic, ghrelin and leptinergic. In this context, the present study aimed to investigate probable feeding responses (eating and drinking) induced by treatment with CST and the GABAAR antagonist bicucullin (BIC) alone or simultaneously (CST + BIC) in the Syrian hibernating hamster (Mesocricetus auratus) model. Hamsters that received these compounds via intracerebroventricular infusions displayed notable variations of feeding and drinking bouts. In particular, an anorexigenic response was evident following treatment with CST while BIC evoked a significant increase of eating and drinking behaviors. Surprisingly when both agents were given simultaneously, a predominating anorexigenic response was detected as shown by evident CST-dependent reduction of feeding bouts. Contextually such behaviors, especially those following the combined treatment were tightly correlated with the significantly increased cerebral dopamine receptor 1 (D1) plus reduced ghrelin receptor (GhsR) and leptin receptor (LepR) transcript levels. Overall, the anorexigenic effect of CST deriving from its tight interaction with GABAARs activity plus D1 and GhsR transcripts tends to propose these neuronal elements as pivotal factors responsible for feeding disorders.