The effects of clozapine on delayed spatial alternation deficits in rats with hippocampal damage.

Full Abstract

Clozapine is an atypical antipsychotic drug that has been shown to improve spatial memory in some animal models; however its efficacy in reversing spatial memory impairment in rats with hippocampal lesions is unknown. To address this issue, we tested the effects of clozapine on delayed spatial alternation deficits in rats with hippocampal damage in three separate experiments. In each experiment, adult male rats received sham surgery or direct stereotaxic infusions of the excitotoxin, NMDA, into the hippocampus. In the first study, seven days after surgery, the sham control animals received daily saline injections while the lesioned animals were split into two groups that received daily saline or clozapine (2.0 mg/kg, sc) injections. During the fifth week of injections, all animals were tested in a food-motivated delayed spatial alternation task. Saline-treated rats with excitotoxic hippocampal damage displayed significant deficits in delayed spatial alternation. Daily clozapine injections completely reversed this deficit. In a second experiment, it was found that clozapine treatment limited to the testing days only did not improve alternation performance in lesioned rats. Finally, in a third experiment, chronic clozapine treatment did not improve alternation performance in lesioned rats that were pre-trained in the alternation task prior to surgery. These results suggest that chronic, but not acute, clozapine treatment enables rats with hippocampal damage to develop new spatial learning, but can not rescue old spatial learning established prior to damage. These results may have implications for the treatment of cognitive deficits caused by hippocampal dysfunction in disorders such as schizophrenia, Alzheimer's disease, and others.

Author information

Author/s: Bardgett, Mark E (ME); Griffith, Molly S (MS); Foltz, Rebecca F (RF); Hopkins, Jessica A (JA); Massie, Christina M (CM); O'Connell, Shannon M (SM);

Affiliation: Department of Psychology, Northern Kentucky University, Highland Heights, KY 41099, USA. bardgettm(-atsign-)nku.edu

Grants: P20 RR16481 (Agency:NCRR NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Neurobiology of learning and memory (Neurobiol Learn Mem), published in United States. (Language: eng)

Reference: 2006-Jan; vol 85 (issue 1) : pp 86-94

Dates: Created 2005/12/19; Completed 2006/03/09; Revised 2007/11/14;

PMID: 16213757, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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