Ovariectomy-mediated impairment of spatial working memory, but not reference memory, is attenuated by the knockout of the dopamine D3 receptor in female mice

• OVX mice show regular spatial reference memory during Morris water maze task.
• D3KO sham-operated mice perform regularly during Morris water maze tasks.
• OVX mice exhibit spatial working memory deficits in Morris water maze.
• Working memory deficits by OVX are attenuated in D3KO mice.

Memory modulation is implemented through many different factors, such as the dopaminergic system and ovarian hormones. Alterations of these factors may cause memory behavior changes. In the current study, dopamine D3 receptor mutant (D3−/−) female mice and their wild-type (WT) controls were used and randomly assigned to ovariectomized (OVX) and sham-operated (Sham) groups (four groups: WT-OVX, WT-Sham, D3−/−-OVX, and D3−/−-Sham). The possibility of co-effects of the dopamine D3 receptor and ovarian hormones on cognitive behavior was then examined. The spatial reference memory (SRM) and the motivation to escape from the water maze were not affected by either knockout of the dopamine D3 receptor or ovariectomy. Knockout of the dopamine D3 receptor had no effect on spatial working memory (SWM) in the Sham groups, but had a positive effect on SWM in the OVX groups. While an ovariectomy inhibited SWM in WT mice, it had no effect on SWM in D3−/− mice. These data suggested that ovarian hormone deprivation may induce spatial working memory decline, and blockade of D3 receptors could ameliorate this impairment. Based on our findings, there may be specific molecular changes responsible for the function of D3 receptors in modulating information processes under conditions of ovarian hormone deficit, which need to be further elucidated.