The International Journal of Neuropsychopharmacology

Thematic Section: Memory and Cognition

Phencyclidine withdrawal disrupts episodic-like memory in rats: reversal by donepezil but not clozapine

Romain Le Cozanneta1, Kevin C. F. Fonea2 and Paula M. Morana1 c1

a1 School of Psychology, University of Nottingham, Nottingham, UK

a2 School of Biomedical Sciences, University of Nottingham, Nottingham, UK


Episodic memory is the capacity to recall an event in time and place (What? Where? When?). Impaired episodic memory is a debilitating cognitive symptom in schizophrenia but is poorly controlled by currently available antipsychotic drugs. Consistent with glutamatergic abnormality in schizophrenia, the NDMA receptor antagonist, phencyclidine (PCP), induces persistent ‘schizophrenia-like’ symptoms including memory deficits in humans and rodents and is widely used as an animal model of the disorder. However, in contrast to humans, PCP and PCP withdrawal-induced memory deficits in rodents are reversed by antipsychotic drugs such as clozapine. One possible explanation is that the memory tasks used in animal studies do not simultaneously test the What? Where? When? components that characterize episodic memory in human tasks. We investigated whether subchronic PCP withdrawal disrupts memory in rats in a task that requires simultaneous integration of memory for object, place and context. Rats learn to discriminate objects under specific spatial and contextual conditions analogous to the What? Where? When? components of human episodic memory. We found that PCP withdrawal impaired performance on this task and that the atypical antipsychotic drug clozapine did not reverse this impairment. However the acetylcholinesterase inhibitor (AChEI) donepezil, which has been shown to improve episodic memory in humans did reverse the effect of PCP. This suggests that PCP withdrawal disruption of object–place–context recognition in rats may prove to be a useful model to investigate episodic memory impairment in schizophrenia and supports the suggestion that AChEIs could prove to be a useful pharmacological strategy to specifically treat episodic memory problems in schizophrenia.

(Received December 08 2009)

(Reviewed January 04 2010)

(Revised February 08 2010)

(Accepted February 09 2010)

(Online publication March 18 2010)


c1 Address for correspondence: Dr P. M. Moran, School of Psychology, University of Nottingham, Nottingham NG7 2RD, UK. Tel.: +44 115 9515312 Fax: +44 115 9515324 Email:

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