Atypical antipsychotics attenuate a sub-chronic PCP-induced cognitive deficit in the novel object recognition task in the rat

• Published in: Behavioural brain research Vol. 184; no. 1; pp. 31 - 38
• Main Authors: Grayson, B., Idris, N.F., Neill, J.C.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 22.11.2007; Elsevier Science
• Subjects: Adult and adolescent clinical studies; Analysis of Variance; Animals; Antipsychotic Agents - therapeutic use; Antipsychotics; Behavior, Animal - drug effects; Behavioral psychophysiology; Biological and medical sciences; Cognition; Cognition Disorders - chemically induced; Cognition Disorders - drug therapy; Cognition Disorders - physiopathology; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Exploratory Behavior - drug effects; Female; Fundamental and applied biological sciences. Psychology; Medical sciences; Motor Activity - drug effects; Neuropharmacology; Novel object recognition; Pharmacology. Drug treatments; Phencyclidine; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Rat; Rats; Recognition (Psychology) - drug effects; Schizophrenia; Schizophrenia; Antipsychotics; Cognition; Phencyclidine; Novel object recognition; Rat; Atypical antipsychotic; Subchronic; Cognitive disorder; Neuroleptic; Psychotropic; Memory; Glutamate receptor; Psychosis; Anesthetic; Piperidine derivatives; Hallucinogen; Antagonist; Rodentia; Neuroprotective agent; Novelty stimulus; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; NMDA receptor; Recognition
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2007.06.012

The novel object recognition (NOR) task is a paradigm employed to detect both disruption and improvement of non-spatial memory in rats. PCP (phencyclidine) may be used to model aspects of schizophrenia symptomology in rats, in particular cognitive deficits. The aim of this study was to investigate the ability of typical and atypical antipsychotics to improve a sub-chronic PCP-induced impairment in cognition using the NOR task. Female hooded-Lister rats (195 ± 12 g) received either vehicle (0.9% saline twice daily) or PCP (2 mg/kg, twice daily) for 7 days followed by 7-days drug free. Haloperidol (0.05 and 0.075 mg/kg), clozapine (1 and 5 mg/kg), risperidone (0.05, 0.1 and 0.2 mg/kg) or vehicle (veh, saline) was administered i.p. 30 min prior to testing. Rats completed an acquisition trial followed by an inter-trial interval of 1 min, then a retention trial. Following sub-chronic vehicle treatment, rats spent significantly ( p < 0.05) more time exploring the novel compared to the familiar object, an effect that was abolished in the sub-chronic PCP treated animals. Clozapine (1.0 and 5.0 mg/kg) and risperidone (0.2 mg/kg) but not haloperidol significantly attenuated the PCP-induced impairment such that animals again spent significantly more time exploring the novel compared with familiar object ( p < 0.05). These results support our earlier work showing that acute PCP induces a robust object recognition deficit in female rats. Clozapine and risperidone but not haloperidol showed efficacy to reverse the deficit induced by sub-chronic PCP suggesting that this test may have some validity for assessing efficacy for improvement of cognitive deficit symptoms of schizophrenia.