Microinjection of a dopamine-D1 receptor agonist into the ventral tegmental area reverses the blocked expression of morphine conditioned place preference by N-methyl-D-aspartate receptor antagonist

Background: The release of dopamine (DA) in the posterior ventral tegmental area (pVTA) plays an important role in cue-related learning, reward, and relapse. On the other hand, studies have shown that the use of N-methyl-D-aspartate receptor (NMDAR) antagonist (AP5) inhibits the expression of morphine (5 mg/kg, s. c) conditioned place preference (CPP). In this study, we have tried to show the interaction effect of the DA stimulatory agents through D1-like receptor (D1R) agonist (SKF38393) and D2-like receptor (D2R) antagonist (eticlopride; through disinhibition) with NMDAR antagonist into the pVTA on the expression of morphine CPP. Materials and Methods: The SKF38393 and eticlopride, individually and simultaneously (in ineffective doses), were injected into the pVTA with the AP5 in rats, and animals were then placed in a CPP apparatus. Results: Concomitant administration of D1R agonist (4 mu g/rat) with NMDAR antagonist (1 mu g/rat) induced the expression of morphine CPP, but the administration of D2R antagonist with NMDAR antagonist was unaffected on the expression of morphine CPP. Furthermore, concomitant administration of ineffective doses of D1R agonist and D2R antagonist with NMDAR antagonist had no effect on the expression of morphine CPP. Conclusions: The results showed using higher doses of D1R agonist with NMDAR antagonist could reverse the blocked expression of morphine CPP by NMDAR antagonists, while, the use of D2R antagonist with NMDAR antagonist could not. Therefore, presynaptic receptors such as D1R probably through releasing other stimulatory neurotransmitters can play a vital role in the expression of morphine CPP and cue-related learning.