Synergistic Activation of the Nitrergic System of the Nucleus Accumbens by Dopamine D1 and D2 Receptor Agonists

Abstract

Vital intracerebral microdialysis studies in Sprague–Dawley rats showed that administration of the dopamine D1 receptor agonist SKF-38393 (100 μM) into the medial segment of the nucleus accumbens induced an increase in the extracellular citrulline (a coproduct of NO synthesis) level in this part of the brain (mean 139 ± 3%) and this was prevented by local administration of the neuronal NO synthase inhibitor 7-nitroindazole (0.5 mM). Administration of the dopamine D2 receptor agonist quinelorane (100, 500, and 1000 μM) into the medial segment of the nucleus accumbens had no effect on this parameter. Simultaneous administration of SKF-38393 and quinelorane (100 μM each) into the medial segment of the nucleus accumbens was accompanied by a significant increase in the extracellular citrulline level in this part of the brain (mean 243 ± 14%) and this was blocked by local administration of 7-nitroindazole (0.5 mM). This study provides the first evidence for the cooperative synergistic regulation by the nitrergic system of the medial segment of the nucleus accumbens by dopamine D1 and D2 receptors.