Hypothermia induced by delta9-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. delta9-Tetrahydrocannabinol (delta9-THC), a potent hypothermic agent, appears to mediate this effect via some central mechanism. The studies reported here suggest that delta9-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 hyperthemia (+2.1degrees +/- 0.1degreesC, p less than 0.01) within 2 hr after surgery when compared to the sham operated controls. delta9-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 delta9-THC administration. The hypothermic response to 5 and 10 mg/kg delta9-THC in the lesioned animals was significantly greater (p less than 0.05) and showed a trend toward longer duration than the hypothermia induced in the sham operated controls. These data demonstrate that delta9-THC is able to induce a hypothermic response in rats whose body temperatures were elevated by POR ablation. Although delta9-THC does not appear to act primarily at POR to induce hypothermia, it is evident than an intact POR plays a role in modifying the duration and magnitude of delta9-THC induced hypothermia.