Morphine alters preproenkephalin gene expression.

Rats made tolerant/dependent to morphine by s.c. implantation of drug pellets displayed a significant decrease in striatal preproenkephalin mRNA that persisted during the period of withdrawal. Levels of Met-enkephalin were normal at the end of treatment, but reduced after withdrawal. The direction and time-course of these alterations are consistent with roles for altered neuronal gene expression in the phenomena of opiate tolerance and dependence.