Effects of Chronic Δ9‐Tetrahydrocannabinol During Adolescence on Adult Repeated Acquisition and Performance Behavior and CB1 Receptor Expression in Male and Female Rats

Abstract

There is evidence that marijuana use during adolescence can result in long‐term learning deficits, and that these deficits may occur in a sex‐specific manner. To examine these effects further, male and female adolescent rats received daily injections of saline or 5.6 mg/kg of Δ9‐tetrahydrocannabinol (THC) for 40 days. This yielded four treatment groups with respect to sex and adolescent treatment (female/saline, female/THC, male/saline, and male/THC). Rats were then trained to respond under a multiple schedule of repeated acquisition and performance of response sequences, and subsequently administered THC acutely to determine adult sensitivity. Brain tissue was collected at two time points and analyzed for CB1 receptor (CB1R) levels by western blot. With respect to the behavioral effects, THC produced both rate‐decreasing and error‐increasing effects in both sexes; however, males were less sensitive than females and there was an equipotent disruption of response rate and percent errors. In females, response rate was disrupted more potently than percent errors. THC administration during adolescence did not alter adult sensitivity for either sex, but it did affect adult expression levels in the hippocampus and striatum despite the lack of CB1R downregulation following chronic treatment. More specifically, adult female subjects had long‐term increases in CB1R levels in both brain regions, whereas the expression pattern in males varied depending on the region. In summary, THC during adolescence was unable to alter the sex‐dependent effects of acute THC on a complex operant task, but it was able to produce long‐term changes in CB1R expression in the adult brain.