Simultaneous activation of the α1A-, α1B- and α1D-adrenoceptor subtypes in the nucleus accumbens reduces accumbal dopamine efflux in freely moving rats

Intra-accumbal infusion of the α1-adrenergic agonist methoxamine, which has comparable affinity for α1A-, α1B- and α1D-adrenoceptor subtypes, fails to alter noradrenaline efflux but reduces dopamine efflux in the nucleus accumbens of rats. In-vivo microdialysis experiments were carried out to analyse the putative contribution of α1A-, α1B- and α1D-adrenoceptor subtypes to the methoxamine-induced decrease in accumbal dopamine efflux in freely moving rats. The drugs used were dissolved in the infusion medium and administered locally through a dialysis membrane. Intra-accumbal infusions of the α1A-adrenoceptor antagonist 5-methylurapidil (6 pmol), the α1B-adrenoceptor antagonist cyclazosin (0.6 and 6 pmol) and the α1D-adrenoceptor antagonist BMY 7378 (0.6 pmol) did not alter accumbal efflux of noradrenaline or dopamine: pretreatment with each of these α1-adrenoceptor subtype-selective antagonists counteracted the methoxamine (24 pmol)-induced decrease in accumbal dopamine efflux. Doses indicated are the total amount of drug administered over a 60-min infusion period. These results clearly suggest that the α1A-, α1B- and α1D-adrenoceptor subtypes in the nucleus accumbens mediate the α1-adrenergic agonist methoxamine-induced decrease in accumbal dopamine efflux. The present study also provides in-vivo neurochemical evidence indicating that concomitant, but not separate, activation of the α1A-, α1B- and α1D-adrenoceptors in the nucleus accumbens is required for α1-adrenergic inhibition of accumbal dopaminergic activity.