title: Chronic pubertal cannabinoid treatment as a behavioural model for aspects of schizophrenia: effects of the atypical antipsychotic quetiapine.
abstract: Chronic pubertal cannabinoid treatment in rats has been suggested for modelling aspects of schizophrenia since it results in long-lasting behavioural alterations reflecting certain characteristics of schizophrenia symptomatology. Lasting deficits in sensorimotor gating, impaired short-term mnemonic processing, reduced motivation as well as inappropriate and deficient social behaviour have been reported after chronic cannabinod treatment during pubertal development. In addition, sensorimotor gating deficits were able to be restored by acute injections of the typical antipsychotic haloperidol. The aim of this study was to examine possible acute as well as lasting beneficial effects of the atypical antipsychotic drug quetiapine in adult animals undergoing chronic treatment of the synthetic cannabinoid receptor agonist WIN 55,212-2 (WIN) (1.2 mg/kg) during puberty. Therefore, animals were tested repeatedly for their performance in social interaction and social recognition after acute and chronic quetiapine treatment. Chronic pubertal WIN treatment induced persistent deficits in social recognition and impaired social interaction. Acute quetiapine treatment was able to completely restore those deficits in social behaviour and social memory. Social recognition memory was affected again 1 wk after cessation of chronic quetapine treatment; however, in social interaction persistent improvements could be detected. In conclusion, the results indicate that the atypical antipsychotic drug quetiapine is able to acutely restore deficits in social behaviour induced by developmental cannabinoid exposure and even exert some persistent beneficial effects. Furthermore, the present data give further support and validity for the suitability of chronic pubertal cannabinoid administration as an animal model for aspects of schizophrenia.
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
authors.forename: F Markus
authors.initials: FM
authors.lastname: Leweke
authors.forename: Miriam
authors.initials: M
authors.lastname: Schneider
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D048588:Benzoxazines / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids / Q000494:pharmacology*; D003987:Dibenzothiazepines / Q000494:pharmacology*; D004195:Disease Models, Animal; D006120:Grooming / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D000069348:Quetiapine Fumarate; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy*; D012741:Sexual Maturation; D012919:Social Behavior; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids; D003987:Dibenzothiazepines; D009025:Morpholines; D009281:Naphthalenes; D000069348:Quetiapine Fumarate; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone