title: Chronic administration of clozapine alleviates reversal-learning impairment in isolation-reared rats.
abstract: Isolation rearing has been used for inducing schizophrenia-like symptoms in rats. Human schizophrenics have deficits in prefrontal-dysfunction-related cognitive/behavioral flexibility. Rats with lesions of the medial prefrontal cortex perform poorly in reversal learning. It is uncertain whether isolation rearing, however, causes reversal-learning impairment in adult rats. Using the rotating T maze, this study examined the effect of chronic administration of clozapine on visual discrimination learning and reversal learning in isolation-reared and socially reared adult rats. The results show that isolation-reared rats without clozapine injection performed significantly worse than socially reared rats in reversal learning but not in acquisition learning. Chronic injection of clozapine (5 or 10 mg/kg) in isolation-reared rats significantly improved reversal learning but had no effects on acquisition learning. Further data analyses show that in both the inhibition phase and the new-strategy-acquisition phase of reversal learning, isolation-reared rats needed significantly more correct-response trials to reach the criterion than socially reared rats, and clozapine significantly reduced the isolation-induced impairment of reversal learning only in the new-strategy-acquisition phase. In socially reared rats, clozapine had a dose-related interfering effect on reversal learning but not acquisition learning. This study supports the use of isolation rearing as a model for investigating the neurodevelopmental hypothesis of schizophrenia.
authors.affiliation: Department of Psychology, Speech and Hearing Research Center, Peking University, Beijing, China.
authors.forename: Nanxin
authors.initials: N
authors.lastname: Li
authors.forename: Xihong
authors.initials: X
authors.lastname: Wu
authors.forename: Liang
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007859:Learning Disabilities / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012193:Reversal Learning / Q000187:drug effects*; D012934:Social Isolation / Q000523:psychology*; D014796:Visual Perception / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine