ANTAGONISM OF THE EFFECTS ON THERMOREGULATION OF Δ9‐TETRAHYDROCANNABINOL BY CLOMIPRAMINE IN THE RAT

Abstract

The effect of pretreatment with clomipramine hydrochloride (15 mg/kg, i.p.) on the (‐)‐trans‐A9‐tetrahydrocannabinol (A9‐THC)‐induced changes in body temperature and brain amines of the rat was investigated. A dose of 0.05 mg/kg of A9‐THC produced hyperthermia and a decrease in whole brain concentration of 5‐hydroxyindoleacetic acid (5‐HIAA). Doses of 2 and 5 mg/kg produced hypothermia and increases in brain 5‐HIAA whereas 0.5 mg/kg did not affect either parameter. A9‐THC, at any of the doses, did not affect the whole brain concentrations of dopamine, noradrenaline or 5‐hydroxytryptamine. Clomipramine modified these responses of A9‐THC in that the dose‐response curves appeared to be shifted to the right. It is concluded that clomipramine acts as an antagonist to these actions of A9‐THC by interfering with entry of A9‐THC into tryptaminergic neurones. 1978 British Pharmacological Society