Neonatal exposure to delta 9-tetrahydrocannabinol enhances sexual responses in the adult male mouse.

From day 1 post partum to postnatal day 5, lactating female mice were given daily oral doses of 25 microliters sesame oil, 0.5 mg tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo(b,d)pyran-1-ol (delta 9-tetrahydrocannabinol; THC)/kg or 50 mg THC/kg in 25 microliters oil. Additionally, the pups were given 20 microliter oil, 10 micrograms testosterone or 20 micrograms testosterone in 20 microliter oil s.c. from days 1 to 5 of age. This regimen resulted in nine treatment groups. At 60 days of age, all males were castrated and their testes weighed. After castration, each mouse was implanted s.c. with a 5 mm length of testosterone-filled silicone elastomer capsule. When adult they were tested for male copulatory behaviour. Following behavioural testing the animals were bled by cardiac puncture for measurement of plasma testosterone levels, and their hypothalami removed and assayed for dopamine, noradrenaline, 5-hydroxytryptamine (5-HT) and LH-releasing hormone (LHRH). In addition, another two groups of pregnant females were given daily oral doses of 0.5 or 50 mg THC/kg or oil during the first 3 or 5 days of lactation. The male pups were either decapitated for collection of trunk blood or homogenized for determination of serum or whole body testosterone concentrations. Neonatal administration of THC altered adult male sexual responses and had no effect on hypothalamic noradrenaline, 5-HT and LHRH concentrations. There were large increases in serum testosterone concentrations in neonates after maternal THC treatment, although these differences were not significant. Additionally, THC did not influence the testosterone content of neonatal tissue or the testosterone concentration of adult plasma. These results suggest strongly that the effect of THC on male sexual responses is not mediated by its effect on adult hypothalamic neurotransmitter concentrations. Some other potential mechanisms are discussed.