Neuroleptic drugs block both the hyperactivity and the increase in caudate nucleus cyclic AMP concentration produced by the administration of tranylcypromine and L-dopa to rats.
Injection of rats with tranylcypromine and L-dopa increased brain dopamine concentrations and produced a behavioural syndrome that includes hyperactivity. It also elevated caudate nucleus cyclic AMP concentrations by approximately 50% in vivo, probably by stimulating dopamine receptors. Pretreatment with chlorpromazine inhibited both the tranylcypromine/L-dopa-induced behaviour and elevated cyclic AMP concentrations in a dose-dependent manner. Haloperidol and alpha-flupenthixol also inhibited both effects, while beta-flupenthixol and pimozide were without effect. Since none of these drugs altered the tranylcypromine/L-dopa-induced rise of brain dopamine, it is likely that they produced their effect by inhibiting dopamine-sensitive adenylate cyclase. A good correlation was found to exist between the neuroleptic inhibition of both the increased behavioural activity and the increased caudate nucleus cyclic AMP concentrations produced by tranylcypromine and L-dopa.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D002421:Caudate Nucleus / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D004298:Dopamine / Q000032:analysis; D007980:Levodopa / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009638:Norepinephrine / Q000032:analysis; D051381:Rats; D014191:Tranylcypromine / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D014150:Antipsychotic Agents; D014191:Tranylcypromine; D007980:Levodopa; D000242:Cyclic AMP; D004298:Dopamine; D009638:Norepinephrine