The effects of dexetimide on pimozide-, haloperidol- and pipamperone-induced inhibition of brain self-stimulation in rats.

Pimozide (0.04, 0.16, 0.63 and 2.50 mg/kg), haloperidol (0.01, 0.04, 0.16 and 0.63 mg/kg) and pipamperone (2.50, 10.0, 40.0 and 160 mg/kg) were given subcutaneously to rats, pressing a lever for brain-stimulation through electrodes implanted in the lateral hypothalamic region of the medial forebrain bundle. The lowest dose of each neuroleptic did not affect self-stimulation; the second dose inhibited the response rate by approximately 50%, whereas the two highest doses completely suppressed self-stimulation behaviour. The centrally acting anticholinergic dexetimide (0.63 mg/kg, s.c.) completly antagonized the pimozide-induced inhibition; the haloperidol-induced inhibition was also completely antagonized except at its highest doses, whereas the effects of the sedative neuroleptic pipamperone were not antagonized. These data are consistent with a presumed dopaminergic cholinergic striatal interaction and show brain self-stimulation to be an effective measure of neuroleptic-anticholinergic interaction.