Suppression of male copulatory behavior by δ9-THC is not dependent on changes in plasma testosterone or hypothalamic dopamine or serotonin content

Abstract

Castrated B6D2 F1 male mice were tested for their sexual responses after being administered 0.5 mg/kg δ 9-tetrahydrocannabinol (THC), 50 mg/kg THC or oil. The animals that received 50 mg/kg, but not 0.5 mg/kg THC, showed deficits in copulatory behavior. Another group of B6D2 F1 castrates were given testosterone propionate (TP) replacement therapy plus 50 mg/kg THC or oil. Similarly, those mice which received 50 mg/kg THC showed behavioral deficits. Lastly, a group of intact B6D2 F1 males were treated with 0.5 mg/kg THC, 50 mg/kg THC or oil, were bled and decapitated, and their brains removed 10 min or 4 hr after treatment. Plasma testosterone (T) and hypothalamic dopamine (DA) levels were unaltered 4 hr after treatment with 50 mg/kg THC, but the concentration of serotonin (5-HT) in their hypothalami was elevated. This effect of THC on hypothalamic 5-HT concentration was not apparent in a larger group of randomly bred animals that were tested. These data strongly suggest that THC's behavioral effects are not mediated by variations in T levels, or by changes in hypothalamic 5-HT or DA concentrations.