Gabriella Ivett, Nambiar Vandana, Kuang Chlinton, Mukundan Abinanda, Dang Jonathan, Venkatraghavan Aneerudh, Stanley B Glenn
Stanley Laboratory, Psychology Department, University of California, Riverside, Riverside, CA, United States.
Stanley Laboratory, Department of Molecular, Cell and Systems Biology, University of California, Riverside, Riverside, CA, United States.
Front Behav Neurosci. 2025 Aug 4;19:1633659. doi: 10.3389/fnbeh.2025.1633659. eCollection 2025.
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 ( = 39) were microinjected with a vehicle or GABA receptor antagonists (bicuculline or picrotoxin) or a GABA 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 ( < 0.001) and picrotoxin ( = 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 ( < 0.001). As for other behaviors, all three of the drugs suppressed resting (bicuculline: < 0.001; picrotoxin: < 0.001; 2-OH saclofen: < 0.01) and increased locomotor activity (bicuculline: < 0.001; picrotoxin: < 0.001; 2-OH saclofen: = 0.02).
Our findings suggest that GABA or GABA 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 and/or GABA receptors are elements of a neurocircuit that participates in the regulation of feeding.
当前肥胖率和饮食失调率一直在稳步上升，凸显了理解进食神经回路的重要性。本研究探讨了一个研究较少的脑区——隔下丘脑核（SHy）在进食控制中的潜在作用。基于一次意外观察，我们假设向SHy中脑内注射γ-氨基丁酸（GABA）受体拮抗剂会引发进食。
成年雄性斯普拉格-道利大鼠（n = 39）被微量注射溶剂、GABA受体拮抗剂（荷包牡丹碱或印防己毒素）或一种GABA受体拮抗剂（2-(S)-(+)-2-羟基-舒氯芬[2-OH舒氯芬]）。在注射后1、2、3和24小时测量食物和水的摄入量，并在1小时内测量行为反应（睡眠、休息、运动活动、剧烈活动和梳理毛发）。
结果显示，与对照组相比，在第2和第3小时注射荷包牡丹碱（P < 0.001）和印防己毒素（P = 0.03）后食物摄入量增加。此外，我们发现注射2-OH舒氯芬1小时后食物摄入量增加（P < 0.001）。至于其他行为，所有三种药物都抑制了休息（荷包牡丹碱：P < 0.001；印防己毒素：P < 0.001；2-OH舒氯芬：P < 0.01）并增加了运动活动（荷包牡丹碱：P < 0.001；印防己毒素：P < 0.001；2-OH舒氯芬：P = 0.02）。
我们的研究结果表明，拮抗剂使GABA或GABA受体失活会引发大鼠进食，并产生延迟效应，同时增加大鼠的总体觉醒。这些研究结果共同表明，表达GABA和/或GABA受体的SHy神经元是参与进食调节的神经回路的组成部分。
