Role of nucleus accumbens μ opioid receptors in the effects of morphine on ERK_1/2 phosphorylation

Rationale: Despite the critical role attributed to phosphorylated extracellular signal regulated kinase (pERK_1/2) in the nucleus accumbens (Acb) in the actions of addictive drugs, the effects of morphine on ERK_1/2 phosphorylation in this area are still controversial. Objectives: In order to investigate further this issue, we studied (1) the ability of morphine to affect ERK_1/2 phosphorylation in the shell (AcbSh) and core (AcbC) of Sprague-Dawley and Wistar rats and of CD-1 and C57BL/6J mice and (2) the role of dopamine D₁ and μ-opioid receptors in Sprague-Dawley rats and CD-1 mice. Methods: The pERK_1/2 expression was assessed by immunohistochemistry. Results: In rats, morphine decreased AcbSh and AcbC pERK_1/2 expression, whereas in mice, increased it preferentially in the AcbSh compared with the AcbC. Systemic SCH 39166 decreased pERK_1/2 expression on its own in the AcbSh and AcbC of Sprague-Dawley rats and CD-1 mice; furthermore, in rats, SCH 39166 disclosed the ability of morphine to stimulate pERK_1/2 expression. Systemic (rats and mice) and intra-Acb (rats) naltrexone prevented both decreases, in rats, and increases, in mice. Conclusions: These findings confirm the differential effects of morphine in rats and mice Acb and that D₁ receptors exert a facilitatory role on ERK_1/2 phosphorylation; furthermore, they indicate that, in rats, removal of the D₁-dependent pERK_1/2 expression discloses the stimulatory influence of morphine on ERK_1/2 phosphorylation and that the morphine’s ability to decrease pERK_1/2 expression is mediated by Acb μ-opioid receptors. Future experiments may disentangle the psychopharmacological significance of the effects of morphine on pERK_1/2 in the Acb.