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 o f mesolimbic alpha-adrenoceptors inhibits the release of mesolimbic dopamin e from alpha-methyl-p-tyrosine-resistant, reserpine-sensitive pools, and th at activation of mesolimbic beta-adrenoceptors stimulates the release of me solimbic dopamine from alpha-methyl-p-tyrosine-sensitive, reserpine-resista nt pools. In the present study we analysed the ability of mesolimbic alpha- and beta-adrenoceptors to modulate the release of dopamine from alpha-meth yl-p-tyrosine-sensitive pools in the nucleus accumbens of high and low resp onders to novelty. Under non-challenged conditions, alpha-methyl-p-tyrosine (10(-4) M, 40 min) produced a decrease in dopamine release that did not di ffer between high and low responders to novelty. The continuous infusion of 10(-6) M isoproterenol (beta-adrenoceptor agonist) diminished the alpha-me thyl-p-tyrosine-induced decrease in dopamine, whereas the continuous infusi on of 10(-5) M phenylephrine (alpha-adrenoceptor agonist) remained ineffect ive. 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 lo w responders to novelty. In general, this study implies that mesolimbic dop amine that is derived from different pools is regulated via different norad renergic receptors. (C) 2000 IBRO. Published by Elsevier Science Ltd. All r ights reserved.