title: Adolescent Cannabinoid Exposure Induces a Persistent Sub-Cortical Hyper-Dopaminergic State and Associated Molecular Adaptations in the Prefrontal Cortex.
abstract: Considerable evidence suggests that adolescent exposure to delta-9-tetrahydrocanabinol (THC), the psychoactive component in marijuana, increases the risk of developing schizophrenia-related symptoms in early adulthood. In the present study, we used a combination of behavioral and molecular analyses with in vivo neuronal electrophysiology to compare the long-term effects of adolescent versus adulthood THC exposure in rats. We report that adolescent, but not adult, THC exposure induces long-term neuropsychiatric-like phenotypes similar to those observed in clinical populations. Thus, adolescent THC exposure induced behavioral abnormalities resembling positive and negative schizophrenia-related endophenotypes and a state of neuronal hyperactivity in the mesocorticolimbic dopamine (DA) pathway. Furthermore, we observed profound alterations in several prefrontal cortical molecular pathways consistent with sub-cortical DAergic dysregulation. Our findings demonstrate a profound dissociation in relative risk profiles for adolescent versus adulthood exposure to THC in terms of neuronal, behavioral, and molecular markers resembling neuropsychiatric pathology.
authors.affiliation: Addiction Research Group.|Department of Anatomy and Cell Biology.
authors.forename: Justine
authors.initials: J
authors.lastname: Renard
authors.affiliation: Addiction Research Group.|Department of Anatomy and Cell Biology.
authors.forename: Laura G
authors.initials: LG
authors.lastname: Rosen
authors.affiliation: Addiction Research Group.|Department of Anatomy and Cell Biology.
authors.forename: Michael
authors.initials: M
authors.lastname: Loureiro
authors.affiliation: Department of Anatomy and Cell Biology.
authors.forename: Cleusa
authors.initials: C
authors.lastname: De Oliveira
authors.affiliation: Department of Anatomy and Cell Biology.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schmid
authors.affiliation: Addiction Research Group.|Department of Anatomy and Cell Biology.|Department of Psychiatry, The Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C1.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Rushlow
authors.affiliation: Addiction Research Group.|Department of Anatomy and Cell Biology.|Department of Psychiatry, The Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C1.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Laviolette
mesh_terms: D000375:Aging; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002186:Cannabinoids / Q000378:metabolism / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D006948:Hyperkinesis / Q000378:metabolism; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000378:metabolism; D012919:Social Behavior
chemical_list: D002186:Cannabinoids; D004298:Dopamine
keywords: adolescence; cannabis; dopamine; prefrontal cortex; ventral tegmental area