Differential effects of neuroleptic and serotonergic drugs on amphetamine-induced hypothermia in mice.

Intraventricular administration of amphetamine in mice produced hypothermia. Pretreatment with the dopaminergic (DA) receptor antagonist haloperidol reduced this response, whereas pretreatment with pimozide, sulpiride or cis-flupentixol did not. The direct DA agonist apomorphine strongly potentiated the hypothermia. Pretreatment with the serotonergic (5-HT) receptor blocker cyproheptadine also potentiated the hypothermia. Depletion of 5-HT in brain by p-chlorophenylalanine and accumulation of 5-HT induced by fluoxetine had no effect. In contrast, stimulation of 5-HT receptors by quipazine reduced the hypothermic effect of amphetamine. The inhibitor of catecholamine synthesis alpha-methyl-p-tyrosine, the alpha-adrenergic blocker phentolamine and the muscarinic antagonist atropine failed to alter the hypothermia. It was concluded that DA and 5-HT mechanisms are involved in amphetamine-induced hypothermia in mice and that these two systems display a functional antagonism.