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

TitleEndocannabinoid genetic variation enhances vulnerability to THC reward in adolescent female mice.
Publication TypeJournal Article
Year of Publication2020
AuthorsBurgdorf CE, Jing D, Yang R, Huang C, Hill MN, Mackie K, Milner TA, Pickel VM, Lee FS, Rajadhyaksha AM
JournalSci Adv
Volume6
Issue7
Paginationeaay1502
Date Published2020 02
ISSN2375-2548
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 Δ-tetrahydrocannabinol (THC). Using a genetic knock-in mouse model (FAAH) 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 (CBR) levels at inhibitory and excitatory terminals in the VTA. These developmental changes collectively increase vulnerability of adolescent female FAAH mice to THC preference that persists into adulthood. Together, these findings suggest that this endocannabinoid genetic variant is a contributing factor for increased susceptibility to cannabis dependence in adolescent females.

DOI10.1126/sciadv.aay1502
Alternate JournalSci Adv
PubMed ID32095523
PubMed Central IDPMC7015690
Grant ListT32 DA039080 / DA / NIDA NIH HHS / United States
R01 DA008259 / DA / NIDA NIH HHS / United States
R01 HL098351 / HL / NHLBI NIH HHS / United States
R01 HL136520 / HL / NHLBI NIH HHS / United States
R01 DA042943 / DA / NIDA NIH HHS / United States
R01 NS052819 / NS / NINDS NIH HHS / United States
R01 DA029122 / DA / NIDA NIH HHS / United States