Effect of neurohumoral modulators on the morphine-induced hyperthermia in non-tolerant rats

Wistar rats from one supplier have been shown to exhibit the atypical body temperature responses to morphine. In contrast to commonly used rats, in which morphine induced dose-dependent changes in body temperature, the initial administration of morphine (5, 10, 20, and 40 mg/kg, s.c.) to rats of this particular strain produced a consistent and prominent hyperthermia. This hyperthermia is mediated via an action on the typical morphine receptors since it was completely prevented by a specific narcotic antagonist, naloxone. Effects of neurohumoral modulators on the hyperthermia have been investigated in these rats. Pretreatment of animals with p-chlorophenylalanine, alpha-methyltyrosine, phenoxybenzamine or propranolol did not alter the hyperthermia. In contrast, the s.c. administration of 1 mg/kg of either tertiary or quaternary anticholinergic drug such as scopolamine, atrophine, methscopolamine and methylatropine significantly inhibited the hyperthermia. These results suggest that morphine causes hyperthermia in some strains of rats by a cholinergic mechanism and the involvement of an adrenergic or serotonergic mechanism in this case appears unlikely.