Auto-titration technique using intracranial self-stimulation and effects of antianxiety drugs.

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.