GABA IN THE NUCLEUS-ACCUMBENS SHELL PARTICIPATES IN THE CENTRAL REGULATION OF FEEDING-BEHAVIOR

We have demonstrated previously that injections of 6,7-dinitroquinoxal ine-2,3-dione into the nucleus accumbens shell (AcbSh) elicits pronoun ced feeding in satiated rats. This glutamate antagonist blocks AMPA an d kainate receptors and most likely increases food intake by disruptin g a tonic excitatory input to the AcbSh, thus decreasing the firing ra te of a population of local neurons. Because the application of GABA a gonists also decreases neuronal activity, we hypothesized that adminis tration of GABA agonists into the AcbSh would stimulate feeding in sat iated rats. We found that acute inhibition of cells in the AcbSh via a dministration of the GABA(A) receptor agonist muscimol or the GABA(B) receptor agonist baclofen elicited intense, dose-related feeding witho ut altering water intake. Muscimol-induced feeding was blocked by coad ministration of the selective GABA(A) receptor blocker bicuculline, bu t not by the GABA(B) receptor blocker saclofen. Conversely, baclofen-i nduced feeding was blocked by coadministration of saclofen, but was no t affected by bicuculline. Furthermore, we found that increasing local levels of GABA by administration of a selective GABA-transaminase inh ibitor, gamma-vinyl-GABA, elicited robust feeding in satiated rats, su ggesting a physiological role for endogenous AcbSh GABA in the control of feeding. A mapping study showed that although some feeding can be elicited by muscimol injections near the lateral ventricles, the ventr omedial AcbSh is the most sensitive site for eliciting feeding. These findings demonstrate that manipulation of GABA-sensitive cells in the AcbSh can have a pronounced, but specific, effect on feeding behavior in rats. They also constitute the initial description of a novel and p otentially important component of the central mechanisms controlling f ood intake.