Antagonism of apomorphine-induced hyperthermia in MAOI-pretreated rabbits as a sensitive model of neuroleptic activity.
Apomorphine induced dose-dependent hyperthermia when applied intravenously to rabbits pretreated with a monoamine oxidase inhibitor. Inhibition of the synthesis of catecholamines (by alpha-MT) did not influence on apomorphine-induced hyperthermia, whereas 5-HT synthesis inhibition (by PCPA) completely abolished the hyperthermic response. Some neuroleptics and a 5-HT receptor blocking agent inhibited the hyperthermia in very low doses. A highly significant correlation was registered between the antagonism of apomorphine hyperthermia of 15 neuroleptics and their clinically useful doses. It is concluded that apomorphine-induced hyperthermia most likely is a result of direct stimulation of dopamine receptors and release of 5-HT, and that abolition of this response represents a very sensitive in-vivo model for neuroleptic substances. Antagonism of apomorphine-induced hyperthermia may be achieved by either dopamine or 5-HT receptor blockade.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000037:antagonists & inhibitors*; D001831:Body Temperature / Q000187:drug effects*; D003864:Depression, Chemical; D004347:Drug Interactions; D005260:Female; D008297:Male; D008954:Models, Biological; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D013997:Time Factors
D014150:Antipsychotic Agents; D008996:Monoamine Oxidase Inhibitors; D001058:Apomorphine