GABA-A and GABA-B receptors mediate feeding elicited by the GABA-B agonist baclofen in the ventral tegmental area and nucleus accumbens shell in rats: Reciprocal and regional interactions

Food intake is significantly increased following administration of GABA-B and GABA-A agonists into the nucleus accumbens (NAC) shell and ventral tegmental area (VTA) with receptor-selective antagonist pretreatment capable of blocking these responses within sites. Regional interactions in feeding studies have been evaluated by administering an antagonist in one site of interest prior to administration of the feeding-active agonist in a second site of interest and have identified important relationships, particularly for opioid–opioid interactions. To evaluate whether regional and reciprocal VTA and NAC shell interactions occur for GABA-mediated feeding, the present study examined whether feeding elicited by the GABA-B agonist, baclofen, microinjected into the NAC shell was dose-dependently blocked by pretreatment with either the GABA-B antagonist, saclofen, or the GABA-A antagonist, bicuculline, into the VTA, and then whether VTA baclofen-induced feeding was dose-dependently blocked by NAC shell pretreatment of either saclofen or bicuculline in rats. Rats were stereotaxically implanted with bilateral pairs of cannulae aimed at the VTA and NAC shell and were assessed for food intake following vehicle and baclofen (200 ng) in each site. Baclofen produced similar magnitudes of increased food intake following VTA and NAC shell treatment. Baclofen administration in the VTA and NAC shell was preceded 20 min earlier with administration of bicuculline (0, 7.5, 75, 150, 300 ng) or saclofen (0, 0.5, 1.5, 3, 5 μg) into the other site with intake measured 1, 2 and 4 h after agonist treatment. VTA saclofen dose-dependently and significantly blocked feeding elicited by NAC shell baclofen. Correspondingly, NAC shell saclofen dose-dependently and significantly blocked feeding elicited by VTA baclofen, indicating a robust and bidirectional GABA-B/GABA-B receptor interaction between sites. Whereas VTA bicuculline significantly blocked the increased feeding elicited by NAC shell baclofen, NAC shell bicuculline reduced but did not block feeding elicited by VTA baclofen, indicating a unidirectional interaction GABA-B/GABA-A receptor interaction between sites. Unlike within-site receptor specificity governing the ability of GABA agonist mediation of food intake, the present study demonstrates that GABA, like opioids, employs a distributed brain network in mediating its ingestive effects, and that under certain circumstances, uses multiple receptor subtypes to underlie its regional effects.

Research Highlights
► Feeding is induced by GABA agonists in nucleus accumbens (NAc) or ventral tegmental area (VTA).
► Antagonism of GABA agonist-induced feeding is receptor-selective within sites.
► VTA GABA-B antagonist pretreatment blocks NAC GABA-B agonist-feeding.
► NAC GABA-B antagonist pretreatment blocks VTA GABA-B agonist-feeding.
► VTA GABA-A antagonist pretreatment blocks NAC GABA-B agonist-feeding.