The role of excitatory and inhibitory neurotransmitters upon opioid-induced feeding in the nucleus accumbens shell and ventral tegmental area in rats

The reciprocal connections between the Nacc shell and ventral tegmental area are implicated in reward processes related to ingestive behavior. The Nacc shell and VTA support μ agonist induced feeding. The present study examined whether excitatory amino acid (EAA) NMDA and AMPA receptor subtypes, as well as GABA_A and GABA_B receptor subtypes are involved in opioid-mediated food intake in the Nacc shell and VTA. Pretreatment in the Nacc shell with the GABA_A selective antagonist, bicuculline, potentiated feeding induced by the μ-selective agonist, DAMGO without altering baseline intake; this enhancement in feeding was reduced by pretreatment with general (naltrexone) or μ-selective (β-FNA) opioid antagonists. In contrast, pretreatment in the Nacc shell with the GABA_B-selective antagonist, saclofen, reduced DAMGO-induced feeding without altering baseline intake. On the other hand, pretreatment in the VTA with either bicuculline or saclofen reduced DAMGO-induced feeding that could not be accounted for by changes in baseline intake. The GABA_B-selective agonist, baclofen, increased food intake when administered into the Nacc shell or the VTA; this effect was reduced by baclofen, but not bicuculline. Pretreatment with naltrexone reduced feeding elicited by saclofen in the VTA, but not in the Nacc shell. The significant feeding response produced by the GABA_A agonist, muscimol, in the Nacc shell was reduced by bicuculline or naltrexone, but not by saclofen pretreatment. However, muscimol failed to produce feeding when administered into the VTA. The EAA agonists, AMPA or NMDA administered into the Nacc shell each increased food intake, effects that were blocked by naltrexone pretreatment. DAMGO-induced feeding elicited from the Nacc shell was significantly enhanced by AMPA co-treatment, which in turn was blocked by pretreatment with either naltrexone or β-FNA. In contrast, co-treatment with NMDA and DAMGO in the Nacc shell reduced food intake. These data demonstrate receptor selective actions of the GABA and EAA receptor subtypes, and the site-specificity of these receptor subtypes upon μ opioid agonist-induced feeding in the Nacc shell and VTA. Further, the EAA and GABA receptor subtypes thereby modulate the opioid mediation of the reward value of food.