Chronic opiate agonists down-regulate prodynorphin gene expression in rat brain.

The effects of long-term administration of opioid agonists on the regulation of prodynorphin gene expression in rat brain were investigated. Chronic intracerebroventricular treatment with the synthetic opioid agonist acting on the kappa receptor, U-50,488H, and the classic mu agonist morphine markedly decreased prodynorphin mRNA levels in hypothalamus, hippocampus and striatum of tolerant rats. Levels of ir-Dynorphin A remained unchanged except in two cases. Chronic exposure to opiates thus appears to induce modifications of the endogenous opioid system, as regards gene expression regulation.