Hippocampal D1-but not D2-like dopamine receptors modulate the phosphorylation of ERK in food deprivation-induced reinstatement of morphine in extinguished rats.

Reinstatement to drug abuse is the most challenging issue in the treatment of addiction. Thus, knowledge of the involved neurobiological mechanisms of reinstatement is a fundamental necessity. There is substantial and crucial evidence that dopamine is implicated in motivational processes such as relapse. Our behavioral results reported that the administration of dopamine receptor antagonists inhibited reinstatement of morphine in food-deprived rats. Previous studies have indicated that the ERK pathway plays a critical role in the cellular responses to stress and reward. Therefore, the purpose of the current study was to evaluate the effect of intra-dentate gyrus administration of dopamine receptor antagonists on the phosphorylation of hippocampal ERK in the reinstatement phase of morphine reward in food-deprived rats. All groups of animals passed conditioned place preference and were bilaterally given different doses of D1- or D2-like dopamine compounds (0.25, 1 and 4 μg/0.5 μl) into the dentate gyrus. Immediately after the reinstatement phase, each animal was euthanized, and the hippocampi were immediately dissected. Then, the p-ERK/ERK ratio was evaluated using Western blot analysis. The principal findings in this study demonstrated that intra-dentate gyrus administration of the highest dose of the D1-like receptor antagonist could enhance the hippocampal p-ERK/ERK ratio in food-deprived rats while the D2-Like receptor antagonist failed to change this ratio.