Stimulation of GABA Receptors in the Lateral Septum Rapidly Elicits Food Intake and Mediates Natural Feeding

The increasing prevalence of obesity and eating disorders makes identifying neural substrates controlling eating and regulating body weight a priority. Recent studies have highlighted the role of the lateral septum (LS) in eating control mechanisms. The current study explored the roles of gamma-aminobutyric acid (GABA) receptors within the LS in the control of food intake. Experiments with a rat model (n ≥ 11/group) showed that LS microinjection of the GABA_A receptor agonist, muscimol, and the GABA_B receptor agonist, baclofen hydrochloride (baclofen), elicited intense, dose-dependent feeding. In contrast, LS pretreatment with the GABA_A receptor antagonist, picrotoxin, markedly reduced the muscimol-elicited feeding, and pretreatment injections with the GABA_B receptor antagonist, 2-hydroxysaclofen (2-OH saclofen), reduced the baclofen evoked response. Next, we showed that picrotoxin injection at the beginning of the dark phase of the light-dark cycle-when rats show a burst of spontaneous eating-reduced naturally occurring feeding, whereas 2-OH saclofen was ineffective. These results indicate that the activation of LS GABA_A and GABA_B receptors strongly stimulates feeding and suggests potential roles in feeding control neurocircuitry. In particular, our evidence indicates that endogenous LS GABA and GABA_A receptors may be involved in mediating naturally occurring nocturnal feeding.