Ichimaru Y, Moriyama M, Gomita Y
Jpn J Pharmacol. 1985 Nov;39(3):331-8. doi: 10.1254/jjp.39.331.
In order to study effects of antianxiety drugs on the threshold of intracranial self-stimulation (ICSS), the auto-titration technique was used in the two lever Skinner box. This procedure consisted of conventional ICSS except the brain stimulation current intensity was decreased after every 20 lever press for ICSS, and the animal could press the another reset lever (at any time) to reset the stimulation current intensity to the preseted level. The current intensity at which the animal pressed the reset lever (reset current) was defined as the threshold of ICSS. Since reset currents that the animals showed were very stable during this experiment, the effects of chlordiazepoxide, diazepam and meprobamate were studied. The reset current was significantly lowered by 5.0 mg/kg chlordiazepoxide, p.o., at 1 hr after administration accompanied by the significant increase of ICSS, and the reset current was significantly lowered by 20.0 mg/kg of chlordiazepoxide. On the other hand, diazepam did not lower the reset current, although a significant increase of ICSS was observed at 1.0 mg/kg, p.o. The reset current was lowered by meprobamate at 100 mg/kg, p.o., accompanied by the increase of ICSS, and a significant increase of ICSS was observed at 200 mg/kg but not accompanied by lowered reset current. From these results, increased susceptibility to the brain stimulation current may be involved in the facilitating effects of chlordiazepoxide and meprobamate on ICSS.
为了研究抗焦虑药物对颅内自我刺激（ICSS）阈值的影响，在双杠杆斯金纳箱中采用了自动滴定技术。该程序包括传统的ICSS，但在每次进行20次ICSS杠杆按压后，脑刺激电流强度会降低，动物可以随时按下另一个重置杠杆，将刺激电流强度重置为预设水平。将动物按下重置杠杆时的电流强度（重置电流）定义为ICSS阈值。由于在该实验中动物表现出的重置电流非常稳定，因此研究了氯氮卓、地西泮和甲丙氨酯的作用。口服5.0mg/kg氯氮卓后1小时，重置电流显著降低，同时ICSS显著增加，20.0mg/kg氯氮卓也使重置电流显著降低。另一方面，地西泮虽口服1.0mg/kg时观察到ICSS显著增加，但未降低重置电流。口服100mg/kg甲丙氨酯可降低重置电流，同时ICSS增加，口服200mg/kg时观察到ICSS显著增加，但重置电流未降低。从这些结果来看，氯氮卓和甲丙氨酯对ICSS的促进作用可能与对脑刺激电流的敏感性增加有关。
