Influence of dopamine D3 receptor knockout on age-related decline of spatial memory

There is evidence indicating that the brain's dopaminergic system is involved in age-associated memory impairment. However, specific roles in this process for the different dopamine receptor subtypes have not been elucidated. The cAMP-response element binding protein (CREB) is one of the cellular molecules that have been strongly implicated in the synaptic plasticity deficits occurring in age-related memory and cognitive impairment. In the present study, dopamine D-3 receptor mutant mice were tested in the Morris water maze task. We found that aged D3 receptor mutant mice perform comparatively better than their even-aged wild-type counterparts in both spatial learning training and a subsequent memory test. The degree of hippocampal CREB phosphorylation is significantly higher in aged D-3 receptor mutants compared to aged wild-type mice, whereas no difference in CREB activation was observed in the prefrontal cortex. These results suggest that blockade of D-3 receptors ameliorates age-related memory decline and that D-3 receptor-regulated CREB signaling in the hippocampus may be involved in these age-associated alterations. (C) 2010 Elsevier Ireland Ltd. All rights reserved.