Hypothermic effects of intraventricular and intravenous administration of cannabinoids in intact and brainstem transected cats

Δ⁹-Tetrahydrocannabinol (Δ⁹-THC, 500 μg in 40 μl), and the synthetic cannabinoid Dimethylheptylpuran (DMHP, 75 μg in 6.0 μl) were injected into ventricles III or IV of chronically implanted unanesthetized cats to determine the effect on body temperature. The hypothermia induced by administration of Δ⁹-THC into ventricle IV was faster in onset and reached a greater maximum than that induced by ventricle HI administration. Five hundred μg (i.v.) of Δ⁹-THC produced significantly less hypothermia than interventricular microinjection.Administration of Δ⁹-THC (2 mg/kg i.v.) to animals with a midcollicular transection produced significant decreases in blood pressure, heart rate, and body temperature when compared to animals receiving vehicle alone. Cats transected at C-1 were utilized to determine the rate at which body temperature was lost in animals unable to temperature regulate. Δ⁹-Tetrahydrocannabinol had no effect in these preparations indicating that direct peripheral mechanisms have little or no role in Δ⁹-THC induced hypothermia. It was further noted that Δ⁹-THC had little effect on blood pressure or heart rate in C-1 transected animals. These findings suggest a caudal brain stem site of action for the hypothermie effect of the cannabinoids.