Long-term cocaine self-administration decreases striatal preproenkephalin mRNA in rhesus monkeys

The consequences of long-term exposure to cocaine on striatal preproenkephalin mRNA were assessed using quantitative in situ hybridization in monkeys that self-administered cocaine for approximately 2 years. Autoradiograms revealed high levels of preproenkephalin hybridization signal in both the caudate and putamen of the dorsal striatum, as well as in the shell and core subdivisions of the nucleus accumbens of drug-naive control monkeys. In general, there was a medial to lateral and ventral to dorsal gradient of preproenkephalin mRNA observed within the striatum of normal controls. Preproenkephalin mRNA was significantly reduced in widespread portions of both the dorsal and ventral striatum following chronic long-term cocaine self-administration when compared with levels in normal controls. These data confirm those observed in human drug abusers and suggest that long-term abuse of cocaine can result in significant alterations in the opioid regulation of striatal efferent neurons.