Regulatory effects of D2 receptors in the ventral tegmental area on the mesocorticolimbic dopaminergic pathway

To investigate the regulatory effects of somatodendritic D2 receptors on th e terminal's extracellular dopamine (DA) concentration, a D2 antagonist (et iclopride) was infused directly into the ventral tegmental area via a micro dialysis probe in chloral hydrate-anesthetized rats. Extracellular DA chang es in both the nucleus accumbens (N ACC) and the medial prefrontal cortex ( mPFC) were monitored. Infusion of 10.0 fM eticlopride had no effect on DA i n the mPFC (110.2 +/- 10.0% of baseline) but significantly increased DA in the N ACC (150.1 +/- 11.7%). Infusion of a higher dose of eticlopride (100. 0 or 1,000.0 fM) significantly augmented the DA in the mPFC (121.1 +/- 7.6 and 180.7 +/- 25.8%, respectively) but surprisingly had no effect on DA in the N ACC (111.5 +/- 7.3 and 104.1 +/- 8.7%, respectively). To further inve stigate whether the bluntness of DA increase in the N ACC was due to DA rec eptor activation in the mPFC, eticlopride or SCH23390 was infused into the mPFC prior to and during intrategmental eticlopride infusion, and the chang e of DA in the N ACC was simultaneously monitored. During intra-mPFC 1.0 nM eticlopride infusion but not during 10.0 nM SCH23390 administration (95.5 +/- 6.1%), intrategmental 1,000.0 fM eticlopride infusion could further ele vate DA in the N ACC (130.0 +/- 4.6%). Our results indicated that (1) the m esolimbic and the mesocortical pathways were under tonic inhibition by soma todendritic D2 receptors; (2) the DA concentration in the N ACC first incre ased and then returned to baseline while the intrategmental infusion dose o f eticlopride increased; and (3) the bluntness of DA increase in the N ACC resulted from the D2 receptor activation in the mPFC.