Gomita Y, Moriyama M, Ichimaru Y, Araki Y
Department of Hospital Pharmacy, Okayama University Medical School, Japan.
Physiol Behav. 1991 Jan;49(1):125-9. doi: 10.1016/0031-9384(91)90242-g.
Each animal was chronically implanted with bipolar electrodes in dorsal central gray matter (DCG) and was trained to press a lever to decrease the DCG-stimulation current. Chlordiazepoxide (5-20 mg/kg, PO), diazepam (2-10 mg/kg, PO) and bromazepam (1-5 mg/kg, PO) produced dose-dependent increases in the DCG-stimulation threshold 1-4 h after administration without affecting motor performance. Meprobamate (200 mg/kg, PO) and pentobarbital (10 mg/kg, PO) also slightly increased the stimulation threshold. Their potency was in the order of bromazepam greater than diazepam greater than chlordiazepoxide greater than pentobarbital greater than meprobamate. The increase in the threshold induced by diazepam (10 mg/kg, PO) was inhibited by the GABA antagonists, bicuculline (1 mg/kg, IP) and picrotoxin (0.1 mg/kg, IP). These results suggest that decreased susceptibility to brain stimulation is involved in suppressing effects of anxiolytic drugs on the escape behavior, and also that the antiaversive action of benzodiazepines may be related to a GABAergic mechanism.
每只动物均在背侧中央灰质(DCG)长期植入双极电极,并训练其按压杠杆以降低DCG刺激电流。氯氮卓(5 - 20毫克/千克,口服)、地西泮(2 - 10毫克/千克,口服)和溴西泮(1 - 5毫克/千克,口服)在给药后1 - 4小时产生剂量依赖性的DCG刺激阈值升高,且不影响运动性能。眠尔通(200毫克/千克,口服)和戊巴比妥(10毫克/千克,口服)也轻微提高刺激阈值。它们的效力顺序为溴西泮大于地西泮大于氯氮卓大于戊巴比妥大于眠尔通。地西泮(10毫克/千克,口服)诱导的阈值升高被GABA拮抗剂荷包牡丹碱(1毫克/千克,腹腔注射)和印防己毒素(0.1毫克/千克,腹腔注射)抑制。这些结果表明,对脑刺激敏感性降低与抗焦虑药物对逃避行为的抑制作用有关,并且苯二氮卓类药物的抗厌恶作用可能与GABA能机制有关。