Adolescent Cannabinoid Exposure Induces a Persistent Sub-Cortical Hyper-Dopaminergic State
posted 04/01/2016
publication Published by Oxford University Press
Adolescent Cannabinoid Exposure Induces a Persistent Sub-Cortical Hyper-Dopaminergic State and Associated Molecular Adaptations in the Prefrontal Cortex
Justine Renard1,2,
Laura G. Rosen1,2,
Michael Loureiro1,2,
Cleusa De Oliveira2,
Susanne Schmid2,
Walter J. Rushlow1,2,3 and
Steven R. Laviolette1,2,3
+Author Affiliations
1Addiction Research Group
2Department of Anatomy and Cell Biology
3Department of Psychiatry, The Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C1
Address correspondence to Steven R. Laviolette, Department of Anatomy and Cell Biology, The Schulich School of Medicine and Dentistry, University of Western Ontario, 468 Medical Science Building, London, Ontario, Canada N6A 5C1. Email: steven.laviolette@schulich.uwo.ca
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.
Key words
adolescence
cannabis
dopamine
prefrontal cortex
ventral tegmental area
