SPECIFIC REDUCTIONS OF STRIATAL PRODYNORPHIN AND D-1 DOPAMINE-RECEPTOR MESSENGER-RNAS DURING COCAINE ABSTINENCE

It is well established that the opioid neuropeptide and dopamine syste ms are altered following the use of cocaine. However very little infor mation is available about their possible involvement during cocaine ab stinence. In the present study, the mRNA expression of the dopamine re ceptors, D-1 and D-2, and the opioid peptides, prodynorphin and proenk ephalin, were analyzed in the rat striatum using in situ hybridization histochemistry. Saline or cocaine (30 mg/kg, i.p.) were administered to rats once daily for 1 or 10 days. To examine cocaine abstinence, an imals were treated for 10 days as described followed by a 10-day drug free period. Acute and intermittent cocaine administration elevated th e prodynorphin mRNA expression in the dorsal striatum, consistent with previous reports, while the abstinent phase resulted in a significant reduction of prodynorphin mRNA levels in the ventrorostral striatum. The D-1-receptor mRNA was decreased in the caudorostral striatum durin g cocaine withdrawal, a finding opposite to the increase observed foll owing a single injection of the drug. Proenkephalin and the D-2-recept or mRNAs were not altered during cocaine abstinence, though proenkepha lin was elevated following acute but not repeated cocaine administrati on. These results show long-term suppression on prodynorphin and D-1-r eceptor systems in specific striatal populations localized mainly in r ostral areas during withdrawal from cocaine. (C) 1998 Elsevier Science B.V.