Hypothermia induced by Δ9-Tetrahydrocannabinol in rats with electrolytic lesions of preoptic region

The preoptic region (POR) is a primary central site for thermoregulation. Bilateral lesions of POR disrupt thermoregulation, and in rats, produce a characteristic syndrome including hyperthermia. Δ⁹-Tetrahydrocannabinol (Δ⁹-THC), a potent hypothermic agent, appears to mediate this effect via some central mechanism. The studies reported here suggest that Δ⁹-THC induces hypothermia at a site other than POR. Male Sprague-Dawley rats were divided into 2 groups, one with subsequently confirmed bilateral POR lesions and a sham operated group. The lesioned animals developed hyperthermia (+2.1° ± 0.1°C, p<0.01) within 2 hr after surgery when compared to the sham operated controls. Δ⁹-THC was administered intraperitoneally (5 and 10 mg/kg). Rectal temperature was recorded at 30 min intervals for 2.5 hr. Both lesioned and nonlesioned rats exhibited hypothermia within 30 min of Δ⁹-THC administration. The hypothermic response to 5 and 10 mg/kg Δ⁹-THC in the lesioned animals was significantly greater (p<0.05) and showed a trend toward longer duration than the hypothermia induced in the sham operated controls. These data demonstrate that Δ⁹-THC is able to induce a hypothermic response in rats whose body temperatures were elevated by POR ablation. Although Δ⁹-THC does not appear to act primarily at POR to induce hypothermia, it is evident that an intact POR plays a role in modifying the duration and magnitude of Δ⁹-THC induced hypothermia.