2-PHENYLAMINOADENOSINE STIMULATES DOPAMINE SYNTHESIS IN RAT FOREBRAININ-VITRO AND IN-VIVO VIA ADENOSINE A(2) RECEPTORS

The adenosine agonist 2-phenylaminoadenosine (PAD) stimulated tyrosine hydroxylase activity in rat striatum in vitro. This effect was select ively blocked by the A(2) antagonist 8-chlorostyrylcaffeine (CSC), sug gesting an A(2) receptor-mediated mechanism. PAD also produced a corre sponding increase in striatal adenylyl cyclase activity. Using an in v ivo model that measures presynaptic effects of drugs at dopamine nerve terminals, intracerebroventricular administration of PAD to rats stim ulated tyrosine hydroxylase activity in striatum in a manner that was selectively blocked by CSC. These results suggest that PAD stimulates adenylyl cyclase and tyrosine hydroxylase activity, with a correspondi ng increase in dopamine synthesis, by activation of presynaptic A(2)-t ype receptors in mammalian forebrain. (C) 1997 Elsevier Science B.V.