Effects of lisuride on body temperature of rats and rabbits: relation to microsomal biotransformation and dopaminergic receptor stimulation.

In rats, lisuride, either administered systemically or intracerebroventricularly induced a dose-related hypothermia. This effect was selectively antagonized by blockade of DA receptors in the CNS but not by inhibition of catecholamine synthesis or blockade of serotoninergic receptors. Also a blocker of "peripheral" DA receptors failed to antagonize the hypothermic effect of lisuride in rats. Induction of rat liver microsomal drug-metabolizing enzymes by phenobarbital counteracted lisuride-induced hypothermia. In rabbits lisuride induced a hyperthermic response which was sensitive to both pimozide and metergoline pretreatment. These findings indicate that stimulation of brain DA receptors involved in thermoregulation is responsible for the changes in body temperature indiced by lisuride in rats and rabbits and that these effects are caused by the drug itself and do not require previous biotransformation into an active metabolite.