An Assessment between D1 Receptor Agonist and D2 receptor Antagonist into the Ventral Tegmental Area on Conditioned Place Preference and Locomotor Activity

Abstract

Background: The release of dopamine (DA) has certain roles in the induction of conditioned place preference (CPP) and motor learning in the ventral tegmental area (VTA). The aim of this study was to investigate the excitatory effects of DA through DA-D1 agonist (SKF38393) and elimination of the inhibitory effects of DA through DA-D2 antagonist (eticlopride) into the VTA and its synergistic effects with an ineffective dose of morphine in the induction of CPP. Materials and Methods: Morphine (2.5 mg/kg; s. c.) did not induce a significant CPP, without any effect on the locomotor activity during the testing phase. SKF38393 (0.125, 0.5, and 1 mug/side) and eticlopride (0.5, 1, and 2 mug/side) individually or simultaneously were microinjected bilaterally into the VTA. Results: The administration of SKF38393 (1 and 2 mug/rat) with ineffective morphine and also without morphine caused CPP on test day, while eticlopride (2 mug/rat) caused CPP with morphine only. Locomotor activity increased in groups receiving D1 agonist and D2 antagonist that presumed to be caused by the reinforcing effect. In addition, the concurrent administration of ineffective doses of D1 agonist and D2 antagonist into the VTA with ineffective morphine caused CPP but not with saline. Conclusions: This study showed that there was a need for morphine to activate the reward circuit through the D2 receptor in the VTA while the administration of the D1 agonist could independently activate the reward circuit. In addition, there was a probable synergistic effect using ineffective doses of D1 and D2 receptors, in the acquisition of morphine-induced CPP.