title: Cannabinoids reward sensitivity in a neurodevelopmental animal model of schizophrenia: a brain stimulation reward study.
abstract: The comorbidity schizophrenia and cannabis has a high prevalence. The consumption of cannabis is ten times higher among schizophrenia patients, suggesting that these patients could be differentially sensitive to its motivational effects. To study this question, we investigated the motivational effects of cannabinoid agonists using the brain stimulation reward paradigm and a neurodevelopmental model of schizophrenia: neonatal ventral hippocampus lesions (NVHL). Using the curve-shift paradigm, we first compared the effect single dose (0.75mg/kg) of amphetamine in sham and NVHL rats on reward and operant responding. Then, in different groups of NVHL and sham rats, we studied the effect of delta-9-tetrahydrocannabinnol (THC, 0.5mg/kg, i.p.) and WIN55,212-2 (WIN, 1 and 3mg/kg, i.p.) Rats were initially trained to self-administer an electrical stimulation to the posterio-medial mesencephalon. Once responding was stable, reward threshold defined as the frequency required to induce a half maximum response rate was measured before and after injection of the drug or the vehicle. Results show that amphetamine enhanced reward in sham and NVHL rats, an effect that was shorter in duration in NVHL rats. THC produced a weak attenuation of reward in sham rats while WIN produced a dose-dependent attenuation in NVHL; the attenuation effect of WIN was blocked by the cannabinoid antagonist, AM251. WIN also produced an attenuation of performance in sham and NVHL rats, and this effect was partially prevented by AM251. These results provide the additional evidence that the motivational effect of cannabinoids is altered in animals with a schizophrenia-like phenotype.
authors.affiliation: Faculté de médecine, Département de Psychiatrie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gallo
authors.affiliation: Faculté de médecine, Département de Neurosciences, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Claude
authors.initials: C
authors.lastname: Bouchard
authors.affiliation: Faculté de médecine, Département de Neurosciences, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Fortier
authors.affiliation: Faculté de médecine, Département de Neurosciences, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Ducrot
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: Pierre-Paul
authors.initials: PP
authors.lastname: Rompré
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D048588:Benzoxazines / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D001930:Brain Injuries / Q000150:complications; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D013759:Dronabinol / Q000008:administration & dosage*; D005260:Female; D006624:Hippocampus / Q000473:pathology; D008297:Male; D009025:Morpholines / Q000008:administration & dosage*; D009042:Motivation / Q000187:drug effects / Q000502:physiology*; D009281:Naphthalenes / Q000008:administration & dosage*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D012559:Schizophrenia / Q000188:drug therapy* / Q000209:etiology; D012646:Self Administration; D013997:Time Factors
chemical_list: D048588:Benzoxazines; D000697:Central Nervous System Stimulants; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; C103505:AM 251; 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; Animal model; Brain stimulation reward; Cannabinoids; Schizophrenia