title: Adolescent Δ(9)-Tetrahydrocannabinol Exposure Alters WIN55,212-2 Self-Administration in Adult Rats.
abstract: Cannabis is the most commonly used illicit drug worldwide, and use is typically initiated during adolescence. The endocannabinoid system has an important role in formation of the nervous system, from very early development through adolescence. Cannabis exposure during this vulnerable period might lead to neurobiological changes that affect adult brain functions and increase the risk of cannabis use disorder. The aim of this study was to investigate whether exposure to Δ(9)-tetrahydrocannabinol (THC) in adolescent rats might enhance reinforcing effects of cannabinoids in adulthood. Male adolescent rats were treated with increasing doses of THC (or its vehicle) twice/day for 11 consecutive days (PND 45-55). When the animals reached adulthood, they were tested by allowing them to intravenously self-administer the cannabinoid CB1-receptor agonist WIN55,212-2. In a separate set of animals given the same THC (or vehicle) treatment regimen, electrophysiological and neurochemical experiments were performed to assess possible modifications of the mesolimbic dopaminergic system, which is critically involved in cannabinoid-induced reward. Behavioral data showed that acquisition of WIN55,212-2 self-administration was enhanced in THC-exposed rats relative to vehicle-exposed controls. Neurophysiological data showed that THC-exposed rats displayed a reduced capacity for WIN55,212-2 to stimulate firing of dopamine neurons in the ventral tegmental area and to increase dopamine levels in the nucleus accumbens shell. These findings-that early, passive exposure to THC can produce lasting alterations of the reward system of the brain and subsequently increase cannabinoid self-administration in adulthood-suggest a mechanism by which adolescent cannabis exposure could increase the risk of subsequent cannabis dependence in humans.
authors.affiliation: Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Scherma
authors.affiliation: Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Dessì
authors.affiliation: Neuroscience Institute, National Research Council of Italy, Section of Cagliari, Cagliari, Italy.|Centre of Excellence 'Neurobiology of Dependence', University of Cagliari, Cagliari, Italy.
authors.forename: Anna Lisa
authors.initials: AL
authors.lastname: Muntoni
authors.affiliation: Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Lecca
authors.affiliation: Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Satta
authors.affiliation: Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Luchicchi
authors.affiliation: Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.|Neuroscience Institute, National Research Council of Italy, Section of Cagliari, Cagliari, Italy.|Centre of Excellence 'Neurobiology of Dependence', University of Cagliari, Cagliari, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Pistis
authors.affiliation: Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, Department of Health and Human Services, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Leigh V
authors.initials: LV
authors.lastname: Panlilio
authors.affiliation: Neuroscience Institute, National Research Council of Italy, Section of Cagliari, Cagliari, Italy.|Centre of Excellence 'Neurobiology of Dependence', University of Cagliari, Cagliari, Italy.
authors.forename: Liana
authors.initials: L
authors.lastname: Fattore
authors.affiliation: Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, Department of Health and Human Services, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldberg
authors.affiliation: Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.|Centre of Excellence 'Neurobiology of Dependence', University of Cagliari, Cagliari, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Fratta
authors.affiliation: Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.|Centre of Excellence 'Neurobiology of Dependence', University of Cagliari, Cagliari, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Fadda
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D048588:Benzoxazines / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000502:physiology; D013759:Dronabinol / Q000008:administration & dosage*; D008297:Male; D009025:Morpholines / Q000008:administration & dosage*; D009281:Naphthalenes / Q000008:administration & dosage*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*; D012646:Self Administration; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
chemical_list: D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D013759:Dronabinol; D004298:Dopamine