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.

The tuberal lateral hypothalamus is a major target for GABAA--but not GABAB-mediated control of food intake.

The lateral hypothalamus (LH) is a site of integration for control mechanisms of feeding behavior as it has extensive reciprocal connections with multiple intrahypothalamic and extrahypothalamic brain areas. Evidence suggests that blockade of ionotropric gamma-aminobutyric acid (GABA) receptors in the LH elicits eating in satiated rats. To determine whether this GABA(A) receptor antagonist effect is specific to the LH, the antagonist picrotoxin was injected into one of six nearby sites and food intake was measured. Picrotoxin at 133 pmol elicited eating in the LH, but not in surrounding sites (thalamus, lateral preoptic area, ventral tegmental area, dorsomedial hypothalamus, and entopeduncular nucleus). More specifically, picrotoxin injected into the tuberal LH (tLH) elicited eating, but was ineffective when injected into the anterior or posterior LH. We also investigated whether GABA(B) receptors in the LH participated in the control of food intake and found that neither blockade nor activation of these receptors under multiple conditions changed food intake. Collectively, our findings suggest that GABA(A) but not GABA(B) receptors in the tLH act to suppress feeding behavior.