The mechanism of action of ? 9 -tetrahydrocannabinol on body temperature in mice

Abstract

The effect of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) on body temperature of the mouse was studied. A dose-response relationship (5–100 mg/kg) for the hypothermic effect of Δ⁹-THC was seen. The investigation as to the mechanism underlying the hypothermic action of Δ⁹-THC was also investigated. The relatively specific dopamine antagonist haloperidol potentiated Δ⁹-THC-induced hypothermia as did the α-adrenoceptor antagonist phenoxybenzamine. However, depletion of serotonin with P-chlorophenylalanine reduced the hypothermic response to Δ⁹-THC as did pretreatment with the serotonin antagonist methysergide. Inhibition of re-uptake of serotonin with clomipramine potentiated the hypothermia following Δ⁹-THC. It is suggested that the hypothermic effect of Δ⁹-THC in the mouse is mediated to a large extent via serotonergic mechanisms.