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 D(3) 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.