Guanosine binding protein (G-protein) coupled adenosine A2 receptors reportedly stimulate dopamine (DA) synthesis in rat striatum, possibly via increased adenylyl cyclase (AC) activity and intracellular adenosine-3’,5’- (cycli^-monophosphate (cAMP) concentration. We report that the adenosine A2 agonist 2-phenylaminnadennsine (2-PAD) stimulates tyrosine hydroxylase activity and DA synthesis in rat striatum in vitro (EC5O = 10 pM). 2-PAD also stimulates AC and cAMP formation in rat striatum in vitro (EC5O = 10 pM), and both effects are blocked by the adenosine A2 antagonist 3,7-dimethyl-1- prnparcylxanthine (DPMX). Using a gamma-butyrolactone (GBL) model, that isolates presynaptic neurons, 2-PAD stimulates DA synthesis in rat striatum in vivo after intracerebrnventricular (icv) injection. These results support the hypothesis that A2 agonists stimulate brain DA synthesis by activating presynaptic G-protein coupled A2 receptors to stimulate AC and cAMP. Sigma (g ) receptors also are proposed to be G-protein coupled and modulate DA synthesis in rat striatum. Novel frans-1-phenyl-3-amino-1,2,3,4- tetrahydronapthalenes (PATs) were synthesized and shown to increase brain DA synthesis by a proposed o (03) receptor. Preliminary binding data, using non-hydrolyzable cuannsine triphosphate, support the hypothesis that the [3h ]- H2PAT-03 sites are G-protein coupled. Using the GBL model, H2PAT stimulates DA synthesis in rat nucleus accumbens in vivo by 175% at 10 pg/kg icv. These results are consistent with autoradiographic mapping that indicate [3h ]-H2PAT binding is highest in nucleus accumbens. Signal transduction pathways for 03 sites are under investigation.