Milani H, Graeff F G
Department of Pharmacology, School of Medicine, Campus USP, Brazil.
Pharmacol Biochem Behav. 1987 Sep;28(1):21-7. doi: 10.1016/0091-3057(87)90005-0.
Earlier results indicate that the neurons of the midbrain central gray (CG) responsible for the elaboration and/or expression of aversive states are tonically inhibited by the GABA-benzodiazepine system. In the present study, chemitrodes were implanted in the medial hypothalamus (MH) of the rat, another aversive area of the brain deeply interrelated with the dorsal CG. Microinjection of the benzodiazepine receptor agonist midazolam raised the aversive threshold of electrical stimulation of the MH in a dose-dependent way, though in only about half of the animals tested. In the remaining rats, midazolam was ineffective. Similar antiaversive effects were caused by the GABA-A receptor agonist THIP. In contrast, microinjection of the GABA-A receptor blocker bicuculline induced aversive-like behavioral and autonomic changes. The effects of bicuculline were antagonized by pretreatment with either THIP or midazolam, the latter being counteracted by the competitive benzodiazepine receptor blocker Ro 15-1788. These results extend to the MH, the hypothesis of GABA-benzodiazepine modulation of neurons integrating aversive motivational states.
早期结果表明，负责厌恶状态的形成和/或表达的中脑中央灰质（CG）神经元受到γ-氨基丁酸-苯二氮䓬系统的紧张性抑制。在本研究中，将化学微电极植入大鼠的内侧下丘脑（MH），这是大脑中另一个与背侧CG深度相关的厌恶区域。微量注射苯二氮䓬受体激动剂咪达唑仑以剂量依赖的方式提高了对MH进行电刺激的厌恶阈值，不过仅在约一半的受试动物中有效。在其余大鼠中，咪达唑仑无效。γ-氨基丁酸A受体激动剂四氢嘧啶也产生了类似的抗厌恶作用。相反，微量注射γ-氨基丁酸A受体阻滞剂荷包牡丹碱会诱发类似厌恶的行为和自主神经变化。荷包牡丹碱的作用可被预先使用四氢嘧啶或咪达唑仑拮抗，后者可被竞争性苯二氮䓬受体阻滞剂Ro 15-1788抵消。这些结果将γ-氨基丁酸-苯二氮䓬对整合厌恶动机状态的神经元的调节假说扩展至MH。
