title: An animal model of female adolescent cannabinoid exposure elicits a long-lasting deficit in presynaptic long-term plasticity.
abstract: Cannabis continues to be the most accessible and popular illicit recreational drug. Whereas current data link adolescence cannabinoid exposure to increased risk for dependence on other drugs, depression, anxiety disorders and psychosis, the mechanism(s) underlying these adverse effects remains controversial. Here we show in a mouse model of female adolescent cannabinoid exposure deficient endocannabinoid (eCB)-mediated signaling and presynaptic forms of long-term depression at adult central glutamatergic synapses in the prefrontal cortex. Increasing endocannabinoid levels by blockade of monoacylglycerol lipase, the primary enzyme responsible for degrading the endocannabinoid 2-arachidonoylglycerol (2-AG), with the specific inhibitor JZL 184 ameliorates eCB-LTD deficits. The observed deficit in cortical presynaptic signaling may represent a neural maladaptation underlying network instability and abnormal cognitive functioning. Our study suggests that adolescent cannabinoid exposure may permanently impair brain functions, including the brain's intrinsic ability to appropriately adapt to external influences.
authors.affiliation: Department of Psychology & Neuroscience Program, University of California Riverside, CA 92521, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Lovelace
authors.affiliation: Biomedical Sciences Program, University of California Riverside, CA 92521, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Corches
authors.affiliation: Department of Psychology & Neuroscience Program, University of California Riverside, CA 92521, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Vieira
authors.affiliation: Department of Psychology & Neuroscience Program, University of California Riverside, CA 92521, USA.
authors.forename: Alex S
authors.initials: AS
authors.lastname: Hiroto
authors.affiliation: Department of Psychological & Brain Sciences, Gill Center for Biomedical Sciences, Indiana University, Bloomington, IN 47405, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Mackie
authors.affiliation: Department of Psychology & Neuroscience Program, University of California Riverside, CA 92521, USA; Biomedical Sciences Program, University of California Riverside, CA 92521, USA. Electronic address: edkorzus@ucr.edu.
authors.forename: Edward
authors.initials: E
authors.lastname: Korzus
mesh_terms: D000818:Animals; D048588:Benzoxazines / Q000633:toxicity; D063386:Cannabinoid Receptor Agonists / Q000633:toxicity; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000378:metabolism; D005260:Female; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D002189:Marijuana Abuse / Q000503:physiopathology* / Q000523:psychology; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000633:toxicity; D009281:Naphthalenes / Q000633:toxicity; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000254:growth & development* / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000502:physiology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D048588:Benzoxazines; C578453:CNR1 protein, mouse; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
keywords: Adolescent cannabis abuse; CB1R; Cannabinoids; LTD; mGluR2/3