Role of nucleus accumbens mu opioid receptors in the effects of morphine on ERK sub(1/2) phosphorylation

Despite the critical role attributed to phosphorylated extracellular signal regulated kinase (pERK sub(1/2)) in the nucleus accumbens (Acb) in the actions of addictive drugs, the effects of morphine on ERK sub(1/2) phosphorylation in this area are still controversial. In order to investigate further this issue, we studied (1) the ability of morphine to affect ERK sub(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 D sub(1) and mu -opioid receptors in Sprague-Dawley rats and CD-1 mice. The pERK sub(1/2) expression was assessed by immunohistochemistry. In rats, morphine decreased AcbSh and AcbC pERK sub(1/2) expression, whereas in mice, increased it preferentially in the AcbSh compared with the AcbC. Systemic SCH 39166 decreased pERK sub(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 sub(1/2) expression. Systemic (rats and mice) and intra-Acb (rats) naltrexone prevented both decreases, in rats, and increases, in mice. These findings confirm the differential effects of morphine in rats and mice Acb and that D sub(1) receptors exert a facilitatory role on ERK sub(1/2) phosphorylation; furthermore, they indicate that, in rats, removal of the D sub(1)-dependent pERK sub(1/2) expression discloses the stimulatory influence of morphine on ERK sub(1/2) phosphorylation and that the morphine's ability to decrease pERK sub(1/2) expression is mediated by Acb mu -opioid receptors. Future experiments may disentangle the psychopharmacological significance of the effects of morphine on pERK sub(1/2) in the Acb.