Atipamezole, an α2-adrenoceptor antagonist, augments the effects of L-DOPA on evoked dopamine release in rat striatum

The effects of atipamezole, an alpha(2)-adrenoceptor antagonist, L-3,4-dihydroxyphenylalanine (L-DOPA) and the combination of these drugs on dopamine overflow were studied in dopaminergic presynaptic terminals of rat caudate and nucleus accumbens. Dopamine overflow evoked by 100 pulses of electrical stimulation of the medial forebrain bundle at a low (20 Hz) and high (50 Hz) frequency was measured by in vivo voltammetry. L-DOPA (15 mg/kg) increased dopamine overflow in the caudate nucleus, but this dose had no effects in the nucleus accumbens. Atipamezole (300 mug/kg) had no effects on its own on dopamine overflow, but it did increase the size of the readily releasable storage pool and the effects of L-DOPA treatment in both structures. The combination of the drugs increased dopamine overflow to a larger extent at high compared to low stimulation frequencies. We conclude that the rat caudate nucleus is more sensitive than the nucleus accumbens to the effects of L-DOPA, and the effects of L-DOPA treatment might be effectively enhanced by antagonism of alpha2-adrenoceptors. (C) 2003 Elsevier Science B.V. All rights reserved.