Evidence that the hypothermic response of mice to delta-9-tetrahydrocannabinol is not mediated by changes in thermogenesis in brown adipose-tissue

DELTA-9-Tetrahydrocannabinol (20 mg/kg i.p.) and propranolol (20 and 50 mg/kg i.p.) produced marked falls in the rectal temperatures of mice kept at an ambient temperature of 22-degrees-C. Propranolol (50 mg/kg i.p.) also decreased the thermogenic activity of brown fat, as measured by a decrease in the level of [H-3]GDP binding to mitochondria obtained from mouse interscapular brown adipose tissue. In contrast, DELTA-9-tetrahydrocannabinol (20 mg/kg i.p.) did not affect mitochondrial GDP binding even though the dose used was one shown previously to depress heat production. GDP binding was also unaffected by this cannabinoid in brown adipose tissue taken from mice that had been kept at 13-degrees-C instead of 22-degrees-C. In mice kept at 34-degrees-C, isoprenaline (0.25 and 1.0 mg/kg s.c.) induced a marked rise in rectal temperature and increased the level of GDP binding to brown fat mitochondria. Propranolol (50 mg/kg i.p.) prevented the hyperthermic response to isoprenaline, the mice becoming hypothermic instead. DELTA-9-Tetrahydrocannabinol (20 mg/kg i.p.) had no effect on isoprenaline-induced hyperthermia. We conclude from these data that there is no significant involvement of brown adipose tissue in the hypothermic response of mice to DELTA-9-tetrahydrocannabinol.