The effects of SCH 23390 and raclopride on cocaine-induced analepsis and EEG arousal in rabbits.

The effects of the dopamine D1 and D2 receptor antagonists on cocaine-induced, cholinergically-mediated analeptic and hippocampal theta activity in anesthetized rabbits were investigated. Cocaine (2 mg/kg, i.v.) reduced by 35% the duration of loss of righting reflex produced by a 25 mg/kg dose of pentobarbital. This shortening of narcosis time was blocked by pretreating the animals with the D1 antagonist, SCH 23390 (0.1 mg/kg) but not with the D2 antagonist raclopride (1-2 mg/kg). Cocaine (5 mg/kg, i.v.) also produced a short burst of increased hippocampal theta activity in urethane-anesthetized rabbits, which was also blocked by SCH 23390 but not by raclopride. An unexpected finding was that raclopride itself, at 2 mg/kg (i.v.), produced a marked activation of theta activity that lasted for 15-20 min. When cocaine was administered after this time it produced a potentiated theta response, both in duration and in magnitude. These results suggest that in the rabbit, cocaine exerts a cholinergically-mediated behavioral and EEG arousal through a D1 dopamine mechanism. The role of the D2 system is less clear but appears to be antagonistic to the D1-mediated response.