Mesolimbic alpha-, but not beta-adrenoceptors control the accumbal release of dopamine that is derived from reserpine-sensitive storage vesicles

Mesolimbic beta-, but not alpha-adrenoceptors control the accumbal release of dopamine that is derived from alpha-methyl-para-tyrosine-sensitive pools of newly synthesized neurotransmitter. The aim of this study was to investigate which of these adrenoceptors control the accumbal release of dopamine that is derived from reserpine-sensitive pools of previously stored neurotransmitter. Rats, that were divided in low-responders and high-responders to novelty, were pretreated with 1 mg/kg of reserpine before the alpha-adrenergic-agent phentolamine or the beta-adrenergic-agent isoproterenol was locally applied into the nucleus accumbens. The original finding that phentolamine and isoproterenol increased accumbal dopamine levels in low-responders and high-responders was replicated. Reserpine reduced the phentolamine-induced increase of accumbal dopamine in both types of rat. However, phentolamine could still increase accumbal dopamine levels in reserpine-treated high-responders, but not anymore in reserpine-treated low-responders. Reserpine did not reduce the isoproterenol-induced increase of accumbal dopamine in any type of rat. This study demonstrates that mesolimbic alpha-, but not beta-adrenoceptors control the accumbal release of dopamine that is derived from reserpine-sensitive storage vesicles. In addition, these data confirm our previous finding that dopamine can still be released from storage vesicles of reserpinized high-responders, but not of reserpinized low-responders. The collected data underline our notion that alpha- and beta-adrenergic drugs may have therapeutic effects in patients suffering from diseases in which accumbal dopamine is involved.