Effects of antipsychotic and antianxiety drugs on the morphine abstinence syndrome in rats.

The effects of representative antipsychotic and antianxiety drugs on the abstinence syndrome in morphine-dependent rats were compared. Groups of 10 to 22 male albino Sprague-Dawley rats (250-300 g) were individually implanted s.c. with either two 75-mg morphine base pellets or two placebo pellets. After 72 hr, chlorpromazine (CPZ 1,2 and 4 mg/kg), haloperidol (0.2, 0.4 and 0.8 mg/kg), thioridazine (10, 20 and 40 mg/kg), chlordiazepoxide (2,4 and 8 mg/kg), diazepam (DPM, 1, 2 and 4 mg/kg) or vehicle was injected s.c. 55 min before precipitation of abstinence with naloxone (1 mg/kg s.c.). Jumping was exacerbated by CPZ (4 mg/kg), chlordiazepoxide (4 and 8 mg/kg) and DPM (1, 2 and 4 mg/kg); haloperidol and thioridazine had no significant effect on this sign. Weight less over 1 hr was decreased by CPZ (4 mg/kg) and DPM (4 mg/kg). Wet-dog shakes were decreased by all doses of haloperidol but increased by chlordiazepoxide (8 mg/kg) and DPM (1, 2 and 4 mg/kg). CPZ (2 and 4 mg/kg) significantly increased the incidence of teeth chattering. Other abstinence signs were not affected in a dose-related manner. Although the antipsychotic agents each decrease dopamine availability at the postsynaptic receptor, this mechanism alone cannot explain their actions on individual signs of abstinence. Perhaps it is therefore time to question how modifying agents can be meaningfully compared in morphine-abstinent rats.