Antagonism of the effects on thermoregulation of delta9-tetrahydrocannabinol by clomipramine in the rat.

1 The effect of pretreatment with clomipramine hydrochloride (15 mg/kg, i.p.) on the (--)-trans-delta9-tetrahydrocannabinol (delta9-THC)-induced changes in body temperature and brain amines of the rat was investigated. 2 A dose of 0.05 mg/kg of delta9-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. delta9-THC, at any of the doses, did not affect the whole brain concentrations of dopamine, noradrenaline or 5-hydroxytryptamine. 3 Clomipramine modified these responses of delta9-THC in that the dose-response curves appeared to be shifted to the right. 4 It is concluded that clomipramine acts as an antagonist to these actions of delta9-THC by interfering with entry of delta9-THC into tryptaminergic neurones.