Relationship between D 1 dopamine receptors, adenylate cyclase, and the electrophysiological responses of rat nucleus accumbens neurons

Abstract

The electrophysiological effects of three selective D1 dopamine (DA) receptor agonists, which exhibit different potencies and efficacies for stimulation of adenylate cyclase, were compared in the rat nucleus accumbens (NAc) using single unit recording and microiontophoretic techniques. The partial agonists SKF75670 and SKF38393, and the full agonist SKF81297 produced nearly identical current-response curves for the inhibition of firing of NAc neurons. In rats acutely depleted of DA by alpha-methyl-p-tyrosine (AMPT) pretreatment, all three D1 agonists enabled the inhibition of firing produced by the selective D2 receptor agonist quinpirole, with SKF38393 exerting the greatest efficacy, followed by SKF81297 and SKF75670. Thus, no apparent relationship was found between the previously reported ability of these compounds to stimulate cyclic adenosine monophosphate (cAMP) production and their ability either to inhibit the firing of NAc neurons or to enable quinpirole-mediated inhibition of firing in DA-depleted rats. In addition, the membrane-permeable cAMP analog 8-bromo-cAMP also caused a current-dependent inhibition of the firing of NAc neurons, but failed to enable quinpirole-mediated inhibition in AMPT-pretreated animals. These results suggest either that only a small percentage of D1 receptors need to be stimulated to produce these electrophysiological effects, or that D1 receptors exist within the rat NAc which are linked to transduction mechanisms other than, or in addition to, adenylate cyclase.