European Journal of Pharmacology 2012-08-05

The α1-, but not α2-, adrenoceptor in the nucleus accumbens plays an inhibitory role upon the accumbal noradrenaline and dopamine efflux of freely moving rats

Tadashi Saigusa, Yuri Aono, Takuya Uchida, Koji Takada, Michel M.M. Verheij, Noriaki Koshikawa, Alexander R. Cools, Tadashi Saigusa, Yuri Aono, Takuya Uchida, Koji Takada, Michel M M Verheij, Noriaki Koshikawa, Alexander R Cools

Index: Eur. J. Pharmacol. 688(1-3) , 35-41, (2012)

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Abstract

In vivo microdialysis was used to analyse the role of the α1- and α2-adrenoceptor subtypes in the regulation of noradrenaline and dopamine efflux in the nucleus accumbens of freely moving rats. Intra-accumbal infusion of α1-adrenoceptor agonist methoxamine (24pmol) failed to alter the noradrenaline efflux, but decreased the dopamine efflux. The intra-accumbal infusion of α1-adrenoceptor antagonist prazosin (6, 600 and 6000pmol) produced a dose-related increase and decrease of the noradrenaline and dopamine efflux, respectively. An ineffective dose of prazosin (6pmol) counteracted the methoxamine (24pmol)-induced decrease of dopamine efflux. The prazosin (6000pmol)-induced increase of noradrenaline efflux, but not the decrease of dopamine efflux, was suppressed by the co-administration of an ineffective dose of methoxamine (0.024pmol). Neither the α2-adrenoceptor agonist clonidine (300pmol) and UK 14,304 (300pmol) nor the α2-adrenoceptor antagonist RX 821002 (0.6, 3, 600 and 6000pmol) significantly affected the accumbal noradrenaline and dopamine efflux. The doses mentioned are the total amount of drug over the 60-min infusion period. The present results show that (1) accumbal α1-adrenoceptors which are presynaptically located on noradrenergic nerve terminals inhibit the accumbal noradrenaline efflux, increasing thereby the accumbal dopamine efflux, (2) accumbal α1-adrenoceptors which are postsynaptically located on dopaminergic nerve terminals inhibit the accumbal dopamine efflux, and (3) accumbal α2-adrenoceptors play no major role in the regulation of accumbal efflux of noradrenaline and dopamine.