title: Chronic cannabinoid exposure during adolescence leads to long-term structural and functional changes in the prefrontal cortex.
abstract: In many species, adolescence is a critical phase in which the endocannabinoid system can regulate the maturation of important neuronal networks that underlie cognitive function. Therefore, adolescents may be more susceptible to the neural consequences of chronic cannabis abuse. We reported previously that chronically exposing adolescent rats to the synthetic cannabinoid agonist CP55,940 leads to impaired performances in adulthood i.e. long-lasting deficits in both visual and spatial short-term working memories. Here, we examined the synaptic structure and function in the prefrontal cortex (PFC) of adult rats that were chronically treated with CP55,940 during adolescence. We found that chronic cannabinoid exposure during adolescence induces long-lasting changes, including (1) significantly altered dendritic arborization of pyramidal neurons in layer II/III in the medial PFC (2) impaired hippocampal input-induced synaptic plasticity in the PFC and (3) significant changes in the expression of PSD95 (but not synaptophysin or VGLUT3) in the medial PFC. These changes in synaptic structure and function in the PFC provide key insight into the structural, functional and molecular underpinnings of long-term cognitive deficits induced by adolescent cannabinoid exposure. They suggest that cannabinoids may impede the structural maturation of neuronal circuits in the PFC, thus leading to impaired cognitive function in adulthood.
authors.affiliation: Laboratoire de Physiopathologie des maladies Psychiatriques, UMR_S894 Inserm, Centre de Psychiatrie et Neurosciences, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Justine
authors.initials: J
authors.lastname: Renard
authors.affiliation: CNRS, UMR 8249, 75005 Paris, France; Brain Plasticity Unit, ESPCI-ParisTech, PSL Research University, 75005 Paris, France.
authors.forename: Tania
authors.initials: T
authors.lastname: Vitalis
authors.affiliation: Laboratoire de Physiopathologie des maladies Psychiatriques, UMR_S894 Inserm, Centre de Psychiatrie et Neurosciences, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Rame
authors.affiliation: Laboratoire de Physiopathologie des maladies Psychiatriques, UMR_S894 Inserm, Centre de Psychiatrie et Neurosciences, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Université Paris Descartes, Faculté de Médecine Paris Descartes, Service Hospitalo Universitaire, Centre Hospitalier Sainte-Anne, 75014 Paris, France.
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Krebs
authors.affiliation: CNRS, UMR 8249, 75005 Paris, France; Brain Plasticity Unit, ESPCI-ParisTech, PSL Research University, 75005 Paris, France.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Lenkei
authors.affiliation: Laboratoire de Physiopathologie des maladies Psychiatriques, UMR_S894 Inserm, Centre de Psychiatrie et Neurosciences, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Gwenaëlle
authors.initials: G
authors.lastname: Le Pen
authors.affiliation: Laboratoire de Physiopathologie des maladies Psychiatriques, UMR_S894 Inserm, Centre de Psychiatrie et Neurosciences, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France. Electronic address: therese.jay@inserm.fr.
authors.forename: Thérèse M
authors.initials: TM
authors.lastname: Jay
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002186:Cannabinoids / Q000633:toxicity*; D002908:Chronic Disease; D003511:Cyclohexanols / Q000633:toxicity*; D003712:Dendrites / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D002189:Marijuana Abuse / Q000473:pathology / Q000503:physiopathology; D008565:Membrane Proteins / Q000378:metabolism; D008839:Microelectrodes; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D017208:Rats, Wistar; D016708:Synaptophysin / Q000378:metabolism; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism
chemical_list: D002186:Cannabinoids; D003511:Cyclohexanols; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C482103:Slc17a8 protein, rat; D016708:Synaptophysin; C569016:Syp protein, rat; D050496:Vesicular Glutamate Transport Proteins; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
keywords: Adolescence; Cannabinoid; Dendrites; Prefrontal structure; Synaptic markers; Synaptic plasticity