Endocannabinoid genetic variation enhances vulnerability to THC reward in adolescent female mice.

ABSTRACT: Adolescence represents a developmental period with the highest risk for initiating cannabis use. Little is known about whether genetic variation in the endocannabinoid system alters mesolimbic reward circuitry to produce vulnerability to the rewarding properties of the exogenous cannabinoid Δ⁹-tetrahydrocannabinol (THC). Using a genetic knock-in mouse model (FAAH^C/A) that biologically recapitulates the human polymorphism associated with problematic drug use, we find that in adolescent female mice, but not male mice, this FAAH polymorphism enhances the mesolimbic dopamine circuitry projecting from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and alters cannabinoid receptor 1 (CB₁R) levels at inhibitory and excitatory terminals in the VTA.

SUBMITTER: Burgdorf CE 

PROVIDER: S-EPMC7015690 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature