Regional enhancement of cannabinoid CB1 receptor desensitization in female adolescent rats following repeated Delta 9-tetrahydrocannabinol exposure

Abstract

BACKGROUND AND PURPOSE
Disruption of the substantial re-organization of the brain during adolescence may be induced by persistent abuse of marijuana. The aim of this study was to determine whether adolescent and adult rats exhibit differential adaptation of brain cannabinoid (CB1) receptors after repeated exposure to Delta 9-tetrahydrocannabinol (THC).

EXPERIMENTAL APPROACH

Rats of both ages and sexes were dosed with 10 mg kg-1 THC or vehicle twice daily for 9.5 days. Subsequently, CB1 receptor function and density were assessed.

KEY RESULTS

In all brain regions, THC treatment produced desensitization and down-regulation of CB1 receptors. While the magnitude of down-regulation did not differ across groups, greater desensitization was evident in the brains of THC-treated female adolescent rats for most regions. Adolescent females showed greater desensitization than adult females in the prefrontal cortex, hippocampus, periaqueductal gray (PAG) and ventral midbrain. In contrast, adolescent males exhibited less desensitization in the prefrontal cortex, hippocampus and PAG, an effect opposite to that seen in females. With the exception of the PAG, sex differences were seen only in adolescents, with greater desensitization in the prefrontal cortex, striatum, hippocampus, PAG, and ventral midbrain of females.

CONCLUSIONS AND IMPLICATIONS

These results suggest that the brains of adolescent females may be particularly vulnerable to disruption of CB1 receptor signalling by marijuana abuse. Alternatively, increased desensitization may reflect protective adaptation. Given the extensive re-organization of the brain during adolescence, this disruption has potential long-term consequences for maturation of the endocannabinoid system.