Clozapine does not induce a motor impairment in operant responding for heat reinforcement

This experiment examined the effects of intraperitoneal (i.p.) clozapine (CLZ) compared to haloperidol (HAL) on operant responding for heat reinforcement in a cold environment (-8 degrees C). Three doses of CLZ (1, 3 and 5 mg/kg) were found to dose-dependently increase responding for heat while lowering core temperature (T(c)) only at the highest dose. Three doses of HAL (0.1, 0.3 and 0.5 mg/kg) dose-dependently decreased operant responding which resulted in a dose-dependent decrease in T(c). The highest dose of CLZ was then tested in two other paradigms: a reinforcement schedule in which heat was available as long as the lever was held down, and a temperature gradient (range 7-45 degrees C) in which access to heat required minimal motor effort. The ad libitum reinforcement schedule still did not provide enough heat to overcome the hypothermic effects of CLZ. However, in the gradient, rats receiving CLZ selected a warmer region of the gradient, and T(c) was higher than that of controls. These data support CLZ's reputation for having minimal motor side effects. Unlike HAL, the hypothermic effects of CLZ appear to be unrelated to effects of the drug on movement.