alpha(2C)-Adrenoceptors modulate the effect of methylphenidate on responserate and discrimination accuracy in an operant test

The present study investigated the role of Lu,,adrenoceptors in the regulat ion 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) p eriod. No food reward was delivered during the dark period (40 s). The alph a (2C)-adrenoceptor knockout mice tended to make fewer total responses and collect less rewards than their controls after saline treatment. However, o nly response accuracy of alpha (2C)-adrenoceptor knockout mice was signific antly lower than that of the control mice. Methylphenidate, a drug blocking dopamine re-uptake and increasing dopamine release, dose-dependently decre ased the number of total responses and collected food rewards in control mi ce but increased those measures in cu,,-adrenoceptor knockout mice. In addi tion, the effect of methylphenidate on discrimination accuracy differed bet ween knockout and control mice. Our results indicate that alpha (2C)-adreno ceptors may regulate dopamine-mediated functions. O (C) 2001 Elsevier Scien ce Inc.