Behavioural NeuroscienceResearch PaperValproic acid reduces spatial working memory and cell proliferation in the hippocampus
Section snippets
Subjects
Adult male Lister Hooded rats (n=20, weight was 220–250 g, Charles River Laboratories) were randomly assigned to control (saline injected) and drug-treated groups. Animals were housed in groups of four under a 12-h light-dark cycle with access to food and water and allowed to habituate in the animal facility for 11 days prior to the start of procedures. Animals were weighed daily and all procedures were carried out in accordance with UK Home Office guidelines and licensing. Animal numbers were
VPA reduces performance in a spatial working memory task
To test the behavioural effect of VPA in a hippocampal dependent task, the performance of drug and control treated animals were compared using the NOL test. Results were assessed by comparing the total time animals spent on objects in either novel or familiar locations in the choice trial, and by calculating the discrimination index for each group. Neither drug-treated nor control groups showed any preference for either object in the familiarization trial (data not shown). In both the
Discussion
Mild to moderate cognitive deficits have been described in adults after use of VPA, the present work confirms that this cognitive effect is reproducible in an animal model. Animals sub-chronically treated with VPA showed an inability to discriminate between an object in a novel location and one in a familiar location. The hippocampus is strongly involved in spatial memory and the NOL test, which uses the natural tendency of rats to explore an object placed in a new position, can only be
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