GABA(A) receptors in the lateral hypothalamus as mediators of satiety and body weight regulation.

In the lateral hypothalamus (LH), the inhibitory amino acid neurotransmitter, GABA, has had a long-standing presumptive role as an inhibitor of food intake. However, minimal investigation has been focused on GABA, especially as compared to the attention received by many peptide transmitters. To begin to address this deficiency in the understanding of the role of GABA in the LH and feeding, we report that antagonism of GABA(A) receptors in the rat LH elicits feeding, consistent with previous findings, and provide evidence for the behavioral selectivity of this effect. We extend previous findings that activation of LH GABA(A) receptors suppresses feeding, in particular by showing that nighttime and deprivation-induced eating are dramatically suppressed. Finally, we show that chronic activation, but not blockade, of the LH GABA(A) receptors leads to a reduction in 24 h food intake with concomitant body weight loss. These data collectively suggest that activation of GABA(A) receptors plays a fundamental role in controlling food intake and body weight, a role that has previously been somewhat underestimated.