Enhancement of the hypothermic response of mice to delta-9-tetrahydrocannabinol by subhypothermic doses of chloropromazine and phentolamine

Pretreatment with subhypothermic doses of chlorpromazine, given directly into the IIIrd cerebral ventricle via a chronically implanted cannula (50 µg) or subcutaneously (0.75 mg/kg), was found to enhance the hypothermie response to delta-9-tetrahydrocannabinol (THC; 5–20 mg/kg i.p.) in unrestrained adult male MF1 mice, kept at 22°C. Subcutaneous pretreatment with a subhypothermic dose of phentolamine (30 mg/kg) had a similar effect, whereas pretreatment with desipramine (10 mg/kg s.c.), mepyramine (2.3 and 11.5 mg/kg s.c.), methysergide (2 mg/kg s.c.), pimozide (1 and 5 mg/kg s.c.) or lignocaine (50 mg/kg s.c.), had no effect. Intracerebroventricular pretreatment with phentolamine was also without effect and it is concluded that this drug interacts with THC at some site located outside the brain. Since, in mg/kg terms, chlorpromazine was more potent in enhancing THC-induced hypothermia when given subcutaneously than when injected into the Illrd ventricle, it too may interact with THC at a peripheral site. Indeed, chlorpromazine and phentolamine may both increase the hypothermie response to THC by antagonizing alpha-adrenoceptors on cutaneous blood vessels, thereby decreasing the capacity of animals to minimise peripheral blood flow by vasoconstriction. Alternatively, since the distribution of chlorpromazine within the brain may well have been less efficient after intraventricular than after subcutaneous injection, the possibility remains that chlorpromazine interacted centrally with THC.