title: Animals with a schizophrenia-like phenotype are differentially sensitive to the motivational effects of cannabinoid agonists in conditioned place preference.
abstract: Cannabis is the most consumed illicit drug worldwide, but among patients with a diagnosis of schizophrenia, this consumption is higher suggesting that they are differentially sensitive to cannabis. We chose to study this problematic using a neurodevelopmental model of schizophrenia: neonatal ventral hippocampus lesions (NVHL). In a first study, we compared the locomotor response to novelty, a mild stress and two doses of amphetamine (0.75 and 1.5 mg/kg) in sham and NVHL rats at post-natal day 35 (PD35) or 56 (PD56). In a second study, we investigated the valence of the motivational effect of Delta-9-tetrahydrocannabinnol (THC, 0.5 mg/kg, i.p.) and the cannabinoid receptor agonist, WIN55,212-2 (WIN, 1 mg/kg, i.p.), using the conditioned place preference paradigm; we used a biased procedure that comprised 12 days of testing with 3 paired-conditioning. The effects of this dose of WIN were also measured on locomotor activity. Results confirmed that the adult NVHL animals displayed a stronger locomotor response to the two doses of amphetamine, but not to novelty and a mild stress. In adult NVHL, but not sham animals, WIN stimulated locomotor activity and produced a conditioned place aversion. At the dose tested, THC tended to produce an aversion in adult sham but not NVHL animals. Taken together these findings show that adult animals with a schizophrenia-like phenotype are differentially sensitive to the motivational effect of cannabinoids.
authors.affiliation: Faculté de médicine, Département de Psychiatrie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Gallo
authors.affiliation: Faculté de médecine, Département de Neurosciences, Université de Montréal, Montréal, Québec, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Bouchard
authors.affiliation: Faculté de médecine, Département de Neurosciences, Université de Montréal, Montréal, Québec, Canada; FRQ-S Research Center in Behavioural Neurobiology, Concordia University, Montréal, Québec, Canada. Electronic address: pierre-paul.rompre@umontreal.ca.
authors.forename: P-P
authors.initials: PP
authors.lastname: Rompré
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D048588:Benzoxazines / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D004195:Disease Models, Animal; D013759:Dronabinol / Q000494:pharmacology; D006624:Hippocampus / Q000293:injuries; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009042:Motivation / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000188:drug therapy*; D013028:Space Perception / Q000187:drug effects*
chemical_list: D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; 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; D013759:Dronabinol; D000661:Amphetamine
keywords: Amphetamine; Cannabinoid; Conditioned place preference; Neonatal ventral hippocampus lesion; Schizophrenia