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.