Chronic morphine exposure and spontaneous withdrawal are associated with modifications of dopamine receptor and neuropeptide gene expression in the rat striatum

The influence of chronic morphine and spontaneous withdrawal on the express ion of dopamine receptors and neuropeptide genes in the rat striatum was in vestigated. Morphine dependence was induced by subcutaneous implantation of two morphine pellets for 6 days. Rats were made abstinent by removal of th e pellets 1, 2 or 3 days before they were killed. The mRNA levels coding fo r D1- and D2-dopamine receptors, dynorphin, preproenkephalin A and substanc e P were determined by quantitative in situ hybridization. The caudate puta men and the nucleus accumbens showed equivalent modifications in dopamine r eceptor and neuropeptide gene expression. After 6 days of morphine, a decre ase in De-dopamine receptor and neuropeptide mRNA levels was observed (- 30 %), but there was no change in D1-dopamine receptor mRNA. In abstinent rats , both D1- and D2-dopamine receptor mRNA levels were decreased 1 day after withdrawal (- 30% compared with chronic morphine). In contrast, neuropeptid e mRNA levels were unaffected when compared with those observed after 6 day s of morphine. During the second and third day of withdrawal, there was a g radual return to the levels seen in the placebo-treated group, for both dop amine receptor and neuropeptide mRNAs. Phenotypical characterization of str iatal neurons expressing mu and kappa opioid receptor mRNAs showed that, in striatonigral neurons, both mRNAs were colocalized with D1-receptor and Dy n mRNAs. Our results suggest that during morphine dependence, dopamine and morphine exert opposite effects on striatonigral neurons, and that effects occurring on striatopallidal neurons are under dopaminergic control. We als o show that withdrawal is associated with a down regulation of the postsyna ptic D1 and D2 receptors.