A comparison of atropine, benztropine and diphenhydramine on the reversal of haloperidol induced suppression of self-stimulation.

Acute haloperidol administration (0.25, 0.5 mg/kg) produced a severe reduction in locomotor activity and operant responding for intracranial self-stimulation in rats. If the rats were also given 10 mg/kg of either diphenhydramine or benztropine, this behavioral inhibition was substantially reversed. Atropine (10 mg/kg), however, did not significantly alter the haloperidol inhibition. In a second study, the rats were tested 30 and 120 minutes after the haloperidol treatment (0.25 mg/kg). Again, diphenhydramine and benztropine but not atropine substantially reversed the haloperidol suppression after 30 minutes. When retested after 120 minutes, however, atropine and benztropine but not diphenhydramine partially reversed the haloperidol suppression. Thus, the present study provides support that diphenhydramine can be effective in reversing haloperidol induced suppression of self-stimulation but for a shorter duration than benztropine.