Neuroleptic-induced hypothermia in mice: lack of evidence for a central mechanism.

The present study investigated the ability of neuroleptic drugs to induce hypothermia in mice when they were administered intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.). Twelve neuroleptics belonging to five chemical classes including phenothiazines, butyrophenones, benzamides, thioxanthenes and diphenylbutylpiperidines were injected i.p. All of them, except benzamides, induced a dose-dependent decrease in rectal temperature. Neuroleptics were administered i.c.v. via cannulae previously implanted in mice to determine whether this response might have a central origin. None of the drugs tested induced hypothermia at doses which did not produce toxic effects. These negative results suggest that neuroleptics act to elicit hypothermia via a peripheral, rather than a central mechanism. Since some neuroleptics possess alpha-adrenolytic properties which could induce hypothermia by promoting vasodilatation, we attempted to antagonize the hypothermia produced by peripheral administration of two neuroleptics with phenylephrine, an alpha-adrenoceptor agonist that does not cross the blood-brain barrier. The hypothermia induced by both chlorpromazine and haloperidol was attenuated by phenylephrine, supporting the view that peripheral alpha-adrenoceptors may mediate neuroleptic-induced hypothermia.