Sex differences in the effects of Δ9-tetrahydrocannabinol on spatial learning in adolescent and adult rats

Like other recreational drugs, cannabinoids may produce different effects in men and women. In this study we measured the effects of Delta(9)-tetrahydrocannabinol (THC) on spatial learning in two groups that are underrepresented in drug research - females and adolescents. In the first experiment, adolescent (postnatal day 30) and adult (postnatal day 70) rats of both sexes were treated subchronically with 5.0 mg/kg THC or vehicle for five consecutive days, Thirty minutes after each daily injection, they were tested on the spatial version of the Morris water maze task. In the second experiment, a separate group of adolescent and adult rats of both sexes was treated with 5.0 mg/kg THC or vehicle daily for 21 days and tested, 4 weeks later, on the spatial version of the water maze. Subchronic THC impaired spatial learning, and this effect was dependent upon both the age and sex of the animals tested. Prior exposure to chronic THC, however, did not cause any long-lasting spatial learning deficits. On the basis of our previous studies in male rats the third experiment assessed the dose-response relationship for the effects of THC on spatial learning and memory in female animals. We found that subchronic THC treatment (2.5, 5.0, or 10.0 mg/kg, intraperitoneally) disrupted learning in both adolescents and adults, but with greater effects at higher doses in adolescents compared with adults. The developmental sensitivity to subchronic THC confirms previous work carried out in our laboratory, and the sex-dependent effects highlight the importance of including females in drug abuse and addiction research.