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.
D000818:Animals; D001921:Brain / Q000502:physiology*; D002090:Butyrophenones / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003864:Depression, Chemical; D003909:Dexetimide / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D006220:Haloperidol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007540:Isonipecotic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D010868:Pimozide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D012653:Self Stimulation / Q000187:drug effects*; D014149:Tranquilizing Agents / Q000494:pharmacology
D002090:Butyrophenones; D007540:Isonipecotic Acids; D010880:Piperidines; D014149:Tranquilizing Agents; D010868:Pimozide; D003909:Dexetimide; C005569:pipamperone; D006220:Haloperidol