Abstract
Previous pharmacological studies have reported that striatal dopamine efflux is negatively modulated not only by presynaptic D2 dopamine autoreceptors but also by striatal D1 dopamine receptors. The present experiments employed
in vivo microdialysis to further examine the ability of widely used benzazepine-class D1 agonists to modulate striatal dopamine efflux. In the present study, both the partial D1 agonist (±)-SKF 38393 (10 μM) and the full D1 agonist (±)-SKF 82958 (10 and 100 μM) significantly reduced striatal dopamine efflux during intrastriatal application. Intrastriatal application of the less active enantiomer, S(−)-SKF 38393 (10 μM) did not decrease striatal dopamine suggesting a selective receptor-mediated mode of action of (±)-SKF 38393. Additional experiments were conducted with the full D1 agonist (±)-SKF 82958 in order to characterize the receptor(s) mediating the observed decrease in dopamine efflux. Neither local application of the D1 antagonist R(+)-SCH 23390 (100 μM) nor local application of the selective D2 antagonist raclopride (5 μM) blocked the ability of (±)-SKF 82958 (10 μM) to decrease striatal dopamine efflux. However, intrastriatal application of the less selective D2 antagonist haloperidol (1 μM) did prevent the decrease in striatal dopamine efflux observed during intrastriatal (±)-SKF 82958 application. The present data suggest that the ability of intrastriatally applied benzazepine-class D1 agonists to decrease striatal dopamine efflux is receptor-mediated, but this action apparently is not mediated at D1 or D2 receptors. There is therefore no indication for an intrastriatal population of D1 receptors capable of modulating dopamine efflux.