The purpose of this study was to determine if chronic administration of Δ9-tetrahydrocannabinol (THC) during adolescence would: 1) modify any sex-specific effects of THC on learning, and 2) affect the development of tolerance to THC as an adult. Male and female rats received daily injections of saline or 5.6 mg/kg of THC from postnatal day 35 to 75, yielding four groups (Female/Saline, Female/THC, Male/Saline, and Male/THC). Rats were then trained on a procedure that assayed both learning and performance behavior and administered 0.32-18 mg/kg of THC acutely as adults (Experiment 1). THC produced rate-decreasing and error-increasing effects in both sexes; however, females were more sensitive to the rate-decreasing effects than males. Rats were then chronically administered 10 mg/kg of THC (Experiment 2). Rats that received THC during adolescence developed tolerance to the rate-decreasing effects more slowly and less completely than rats that received saline; in addition, females developed tolerance to the error-increasing effects of THC slower than males. Western blot analysis of brain tissue indicated that there were long-term changes in hippocampal and striatal CB1R levels despite levels that were indistinguishable immediately following chronic treatment during adolescence. Striatal CB1R levels were increased in adult rats that received THC during adolescence; hippocampal CB1R levels varied by sex. In summary, female rats were more sensitive than males to the acute and chronic effects of THC, and chronic administration of THC during adolescence produced long-term changes in CB1R levels that correlated with decreased tolerance development to the rate-decreasing effects of THC.
- The American Society for Pharmacology and Experimental Therapeutics