Chronic intracerebroventricular cocaine differentially affects prodynorphin gene expression in rat hypothalamus and caudate-putamen.

We investigated the effects of sustained administration of cocaine on the regulation of prodynorphin gene expression in rat brain. Intracerebroventricular (i.c.v.) infusion of cocaine hydrochloride (30 micrograms/day) for 7 days, by means of osmotic minipumps, elicited a significant 35% decrease of prodynorphin mRNA levels in rat hypothalamus and increase (22%) in caudate-putamen. At the same time and in the same animals, no significant changes were detected in the hippocampus or in the nucleus accumbens. These results indicate that continuously infused cocaine is able to modulate expression of the prodynorphin gene in opposite directions or has no effect on prodynorphin expression, depending on the brain region analysed. Cocaine, as well as opiates, might activate specific neuronal pathways, shared by different classes of drugs of abuse, involving, at least in part, the endogenous opioid system.