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ORIGINAL RESEARCH article

Front. Behav. Neurosci.

Sec. Motivation and Reward

Volume 19 - 2025 | doi: 10.3389/fnbeh.2025.1633659

GABA Receptor Antagonism Elicits Feeding in the Septohypothalamic Nucleus

Provisionally accepted
Ivett  GabriellaIvett Gabriella*Vandana  NambiarVandana NambiarChlinton  KuangChlinton KuangAbinanda  MukundanAbinanda MukundanJonathan  DangJonathan DangAneerudh  VenkatraghavanAneerudh VenkatraghavanB  Glenn StanleyB Glenn Stanley
  • University of California, Riverside, Riverside, United States

The final, formatted version of the article will be published soon.

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 hours after injection, and behavioral responses (sleeping, resting, locomotor activity, vigorous activity, and grooming) were measured for 1 hour. 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.

Keywords: Septohypothalamic Nuclei, gaba receptors, feeding, Behavioral Responses, Picrotoxin, Bicuculline, Saclofen

Received: 23 May 2025; Accepted: 15 Jul 2025.

Copyright: © 2025 Gabriella, Nambiar, Kuang, Mukundan, Dang, Venkatraghavan and Stanley. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Ivett Gabriella, University of California, Riverside, Riverside, United States

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