GABA receptor antagonism elicits feeding in the septohypothalamic nucleus

Current rates of obesity and eating disorders have been steadily increasing, highlighting the importance of understanding the neural circuits of eating. This study explores the potential role of an understudied brain region, the septohypothalamic nucleus (SHy), in feeding control. Based on a serendipitous observation, we hypothesized that central injections of gamma-aminobutyric acid (GABA) receptor antagonists in the SHy would elicit feeding.

Adult male Sprague-Dawley rats (n = 39) were microinjected with a vehicle or GABA_A receptor antagonists (bicuculline or picrotoxin) or a GABA_B receptor antagonist (2-(S)-(+)-2-hydroxy-saclofen [2-OH saclofen]). Food and water intakes were measured at 1, 2, 3, and 24 h after injection, and behavioral responses (sleeping, resting, locomotor activity, vigorous activity, and grooming) were measured for 1 h.

Results showed increased food intake after bicuculline (p < 0.001) and picrotoxin (p = 0.03) injections during the 2nd and 3rd hours compared to controls. In addition, we found increased food intake 1 hour after 2-OH saclofen injections (p < 0.001). As for other behaviors, all three of the drugs suppressed resting (bicuculline: p < 0.001; picrotoxin: p < 0.001; 2-OH saclofen: p < 0.01) and increased locomotor activity (bicuculline: p < 0.001; picrotoxin: p < 0.001; 2-OH saclofen: p = 0.02).

Our findings suggest that GABA_A or GABA_B receptor deactivation by antagonists elicited eating with a delayed effect and increased general arousal in rats. These findings collectively suggest that SHy neurons expressing GABA_A and/or GABA_B receptors are elements of a neurocircuit that participates in the regulation of feeding.