The Effects of a Selective D2 Dopamine Receptor Agonist and Antagonist on D2 Autoreceptor-Mediated Inhibition of Dopamine Release in the Mouse Nucleus Accumbens

This study examined the function of D2 autoreceptors under the influence of a selective dopamine D2 receptor agonist (quinpirole) and antagonist (sulpiride). Inhibition of medial forebrain bundle (MFB) stimulation-evoked dopamine release by activation of D2 autoreceptors was investigated in the nuclues accumbens (NAc) of urethane-anesthetized mice using fixed potential amperometry. Trains of electical stimulation (5-40 pulses at 15 Hz) were applied to the MFB to endogenously activate D2 autoreceptors. Systemic administration of sulpiride blocked D2 autoreceptor-mediated inhibition of dopamine release in the NAc. Intra-NAc microinfusion of quinpirole by itself did not affect D2 autoreceptor-mediated inhibition of dopamine release. However, following pretreatment with sulpiride, intra-NAc microinfusions of quinpirole were effective in augmenting D2 autoreceptor-mediated inhibition of dopamine release. Together, these results suggest that short-term blockade of D2 autoreceptors in the NAc by a selective D2 receptor antagonist enhances the response of these receptors to a selective D2 agonist