alpha(2C)-Adrenoceptors modulate the effect of methylphenidate on response rate and discrimination accuracy in an...

The present study investigated the role of alpha(2C)-adrenoceptors in the regulation of activity and discrimination accuracy in an operant chamber test. We trained food deprived control and alpha(2C)-adrenoceptor knockout mice to collect liquid food rewards in an operant chamber during the light (20 s) period. No food reward was delivered during the dark period (40 s). The alpha(2C)-adrenoceptor knockout mice tended to make fewer total responses and collect less rewards than their controls after saline treatment. However, only response accuracy of alpha(2C)-adrenoceptor knockout mice was significantly lower than that of the control mice. Methylphenidate, a drug blocking dopamine re-uptake and increasing dopamine release, dose-dependently decreased the number of total responses and collected food rewards in control mice but increased those measures in alpha(2C)-adrenoceptor knockout mice. In addition, the effect of methylphenidate on discrimination accuracy differed between knockout and control mice. Our results indicate that alpha(2C)-adrenoceptors may regulate dopamine-mediated functions.