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In the striatum, dopamine D₁ and adenosine A_2A receptors stimulate the production of cAMP, which is involved in neuromodulation and long-lasting changes in gene expression and synaptic function. Positive coupling of receptors to adenylyl cyclase can be mediated through the ubiquitous GTP-binding protein Gα_S subunit or through the olfactory isoform, Gα_olf, which predominates in the striatum. In this study, using double in situ hybridization, we show that virtually all striatal efferent neurons, identified by the expression of preproenkephalin A, substance P, or D₁ receptor mRNA, contained high amounts of Gα_olf mRNA and undetectable levels of Gα_s mRNA. In contrast, the large cholinergic interneurons contained both Gα_olf and Gα_stranscripts. To assess the functional relationship between dopamine or adenosine receptors and G-proteins, we examined G-protein levels in the striatum of D₁ and A_2A receptor …