The role of caudate nucleus dopamine and cyclic amp in the hyperpyrexia induced by licl plus tranylcypromine in rats

Abstract

Tranylcypromine (TCP), a monoamine oxidase inhibitor, induced a hyperpyrexia in rats which had been given repeated doses of LiCl. This hyperpyrexia was not prevented by the pretreatment with α-adrenergic blockers (phenoxybenzamine and phentolamine), β-adrenergic blocker (DL-propranolol), histamine blockers (promethazine and diphenhydramine), anticholinergic agent (atropine), inhibitors of prostaglandin synthesis (acetylsalicylic acid and sodium salicylate). Among the dopamine (DA) blockers tested, chlorpromazine, thioridazine, fluphenazine, perphenazine and haloperidol, all of which are reported to inhibit the DA-sensitive adenylate cyclase, prevented the hyperpyrexia. On the other hand, sulpiride and metoclopramide, which are reported not to inhibit the DA-sensitive adenylate cyclase, were without effects on the hyperpyrexia. The hyperpyrexia was potentiated by injection of theophylline, a nucleotide phosphodiesterase inhibitor. The cyclic AMP level in the caudate nucleus was significantly increased only when TCP produced the hyperpyrexia in the LiCl-pretreated rats. The cyclic AMP level in the hypothalamus remained unchanged. These results suggest that DA produced the hyperpyrexia by mediation of the cyclic AMP in the caudate nucleus, but not in the hypothalamus.