title: Juvenile cannabinoid treatment induces frontostriatal gliogenesis in Lewis rats.
abstract: Cannabis abuse in adolescence is associated with a broad array of phenotypical consequences, including a higher risk for schizophrenia and other mental disturbances related to dopamine (DA) imbalances. The great variability of these sequelae likely depends on the key influence of diverse genetic vulnerability factors. Inbred rodent strains afford a highly informative tool to study the contribution of genetic determinants to the long-term effects of juvenile cannabinoid exposure. In this study, we analyzed the phenotypical impact of the synthetic cannabinoid agonist WIN 55,212-2 (WIN; 2mg/kg/day from postnatal day 35-48) in adolescent Lewis rats, an inbred strain exhibiting resistance to psychotomimetic effects of environmental manipulations. At the end of this treatment, WIN-injected animals displayed increased survival of new cells (mainly oligodendroglia precursors) in the striatum and prefrontal cortex (PFC), two key terminal fields of DAergic pathways. To test whether these changes may be associated with enduring behavioral alterations, we examined the consequences of adolescent WIN treatment in adulthood (postnatal days 60-70), with respect to DA levels and metabolism as well as multiple behavioral paradigms. Rats injected with WIN exhibited increased turnover, but not levels, of striatal DA. In addition, cannabinoid-treated animals displayed increases in acoustic startle latency and novel-object exploration; however, WIN treatment failed to induce overt deficits of sensorimotor gating and social interaction. These results indicate that, in Lewis rats, juvenile cannabinoid exposure leads to alterations in frontostriatal gliogenesis, as well as select behavioral alterations time-locked to high DAergic metabolism, but not overt schizophrenia-related deficits.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, 1251 Wescoe Hall Dr, Malott Hall, Room 5040, Lawrence, KS, USA; Consortium for Translational Research on Aggression and Drug Abuse (ConTRADA), University of Kansas, Lawrence (KS), USA. Electronic address: bortolato@ku.edu.
authors.forename: Marco
authors.initials: M
authors.lastname: Bortolato
authors.affiliation: "Guy Everett" Laboratory, Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bini
authors.affiliation: "Guy Everett" Laboratory, Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Frau
authors.affiliation: "Guy Everett" Laboratory, Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Devoto
authors.affiliation: "Guy Everett" Laboratory, Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pardu
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada; Department of Medicine (Neurology), University of Manitoba, Winnipeg, MB, Canada. Electronic address: msolbrig2@hsc.mb.ca.
authors.forename: Marylou V
authors.initials: MV
authors.lastname: Solbrig
mesh_terms: D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology; D002186:Cannabinoids / Q000009:adverse effects*; D002470:Cell Survival / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009457:Neuroglia / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D010641:Phenotype; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology; D065808:Prepulse Inhibition / Q000187:drug effects / Q000502:physiology; D011917:Rats, Inbred Lew; D055139:Sensory Gating / Q000187:drug effects / Q000502:physiology; D012919:Social Behavior
chemical_list: D048588:Benzoxazines; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D004298:Dopamine
keywords: Adolescent exposure; Cannabinoids; Dopamine; Gliogenesis; Lewis rats