Preferential enhancement of working memory in mice lacking adenosine A2A receptors

Abstract

There is evidence that adenosine acting at A2A receptors (A2AR) can influence striatal plasticity and cognitive functions. We examined spatial working memory in wild-type (WT) and A2A receptor knock-out (KO) mice using two assessments: the eight arm radial maze and a repeated trial Morris water maze (MWM) paradigm. Compared to WT littermates, A2AR KO mice displayed enhanced working memory as evidenced by a decrease in escape latency in trial 2 compared to trial 1 in the repeated trial MWM, and by a reduction in working memory errors in the radial arm maze. Both MWM and radial maze results indicated that this enhancement of working memory in A2AR KO mice was selective for this specific short-term memory. The decrease in escape latency in MWM was detected with an inter-trial interval of 15 s but not with intervals of 10 or 60 min. In the radial maze, spatial reference memory and memory retention after prolonged training (15 days but not 6 days) were not affected by the A2AR KO. These results demonstrate preferential improvement in spatial working memory by genetic inactivation of the A2AR and support a modulatory role of the A2AR in spatial working memory in mice.