Newly synthesized dopamine in the nucleus accumbens is regulated by β-adrenergic, but not α-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. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.