Newly synthesized dopamine in the nucleus accumbens is regulated by beta-adrenergic, but not alpha-adrenergic, receptors.

Previous microdialysis studies have led to the hypothesis that activation of mesolimbic alpha-adrenoceptors inhibits the release of mesolimbic dopamine from alpha-methyl-p-tyrosine-resistant, reserpine-sensitive pools, and that activation of mesolimbic beta-adrenoceptors stimulates the release of mesolimbic dopamine from alpha-methyl-p-tyrosine-sensitive, reserpine-resistant pools. In the present study we analysed the ability of mesolimbic alpha- and beta-adrenoceptors to modulate the release of dopamine from alpha-methyl-p-tyrosine-sensitive pools in the nucleus accumbens of high and low responders to novelty. Under non-challenged conditions, alpha-methyl-p-tyrosine (10(-4)M, 40 min) produced a decrease in dopamine release that did not differ between high and low responders to novelty. The continuous infusion of 10(-6)M isoproterenol (beta-adrenoceptor agonist) diminished the alpha-methyl-p-tyrosine-induced decrease in dopamine, whereas the continuous infusion of 10(-5)M phenylephrine (alpha-adrenoceptor agonist) remained ineffective. It is concluded that the release of mesolimbic dopamine from alpha-methyl-p-tyrosine-sensitive, reserpine-resistant pools is under excitatory control of beta-adrenergic, but not alpha-adrenergic, receptors in both high and low responders to novelty. In general, this study implies that mesolimbic dopamine that is derived from different pools is regulated via different noradrenergic receptors.