LONG-TERM COCAINE SELF-ADMINISTRATION DECREASES STRIATAL PREPROENKEPHALIN MESSENGER-RNA IN RHESUS-MONKEYS

The consequences of long-term exposure to cocaine on striatal preproen kephalin mRNA were assessed using quantitative in situ hybridization i n monkeys that self-administered cocaine for approximately 2 years. Au toradiograms revealed high levels of preproenkephalin hybridization si gnal in both the caudate and putamen of the dorsal striatum, as well a s in the shell and core subdivisions of the nucleus accumbens of drug- naive control monkeys. In general, there was a medial to lateral and v entral 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 re sult in significant alterations in the opioid regulation of striatal e fferent neurons. (C) 1997 Elsevier Science Inc.