Antagonism of the D1- and D2-like dopamine receptors in the nucleus accumbens attenuates forced swim stress- and morphine priming-induced reinstatement of extinguished rats

Dopaminergic pathways from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) play a critical role in reward-related phenomena as well as in the reinstatement of drug-seeking behavior. Stress is a major trigger for inducing reinstatement, however, the interaction between stress and the dopaminergic system is not well known. The present study was undertaken to investigate the effect of D1- and D2-like dopamine receptors within the NAc in forced swim stress (FSS)- and priming-induced reinstatement of morphine-seeking behaviors. The conditioned place preference (CPP) was induced by injecting morphine (5 mg/kg, SC for 3 days) and lasted for eight days after cessation of the morphine treatment. The FSS (6 min) and effective priming dose of morphine (1 mg/kg, sc) reinstated the extinguished morphine-induced CPP. In order to investigate the effect of intra-accumbal injection of SCH23390 as a D1-like receptor antagonist, or Sulpiride as a D2-like receptor antagonist on the FSS-induced reinstatement of morphine extinguished rats, animals received bilaterally intra-NAc injection of SCH23390 or Sulpiride (0.25, 1 and 4 μg/side) before application of FSS, and then, they were tested in the reinstatement day. Our results showed that the intra-accumbal administration of D1- and D2-like receptors antagonists dose-dependently blocked the effect of FSS on the reinstatement and significantly modulated morphine priming-induced reinstatement as well. These findings suggested that the D1- and D2-like dopamine receptors in the NAc involve in morphine-seeking behaviors and antagonism of these receptors can reduce the effect of stress on rewarding properties of morphine.