The dopamine D1 but not D3 receptor plays a fundamental role in spatial working memory and BDNF expression in prefrontal cortex of mice

Although dopamine within the prefrontal cortex has been implicated in working memory, how different dopamine receptor subtypes contribute to this process need to be further characterized. Previous studies have suggest the importance of dopamine receptors signaling in regulating the brain-derived neurotrophic factor (BDNF) function that is associated with synaptic plasticity underlying normal memory formation. Changes in BDNF expression through the dopamine receptors within the prefrontal cortex may accompany and mediate the spatial working memory. To test the possibility, dopamine D1 and D3 receptor mutant mice were tested in Morris water maze for spatial working memory. We found that trial-dependent, matching-to-sample, learning of the platform location, an index of short-term spatial working memory in mice, was significantly impaired in D1 receptor knockout mice compared to wild-type mice, and regular performance of D3 receptor mutants was observed in the similar working memory task. BDNF protein was significantly decreased in prefrontal cortex, though not in hippocampus, of the D1 receptor knockout mice, whereas no changes were found in both prefrontal cortex and hippocampus of D3 receptor knockout mice. These data suggest that dopamine D1 but not D3 receptors are critical for prefrontal cortex BDNF expression which may be related to spatial working memory processes.

► D1KO mice exhibit working memory deficits during Morris water maze task.
► D3KO mice show regular spatial working memory during Morris water maze task.
► The decreased PFC BDNF levels are found in D1KO mice with working memory deficits.