MU-OPIOID RECEPTOR MESSENGER-RNA IN NUCLEUS-ACCUMBENS IS ELEVATED FOLLOWING DOPAMINE-RECEPTOR ACTIVATION

We have previously demonstrated that continuous cocaine treatment for three days induces a marked but transient increase in mu opioid recept or (MOR) mRNA in nucleus accumbens (n. acc.); SCH 23390 and eticloprid e, selective antagonists of D1- and D2-like dopamine (DA) receptors, r espectively, blocked this cocaine-induced upregulation of MOR mRNA in n. acc. suggesting involvement of both subfamilies of DA receptors in the effect of cocaine (1,2). In the present study the ability of the s elective DA D3 receptor antagonist, nafadotride (3,4), to prevent the cocaine-induced upregulation of MOR mRNA in n. acc. has been examined. Also, regulation of MOR mRNA following chronic administration of the DA agonists, SKF 38393, R((+))-6-Bromo-APB hydrobromide, or bromocript ine, has been studied. Male Sprague-Dawley rats were treated for 3 day s with saline, cocaine, the Db receptor agonists or antagonist deliver ed by osmotic minipump. Expression of MOR mRNA in n. acc. was estimate d by quantitative competitive polymerase chain reaction (PCR) assays f ollowing reverse transcription. Nafadotride (1.0 mg/kg/day) prevented the cocaine-induced upregulation of MOR mRNA in n. acc. When administe red alone, nafadotride did not change the expression of MOR mRNA. The levels of MOR mRNA were elevated in n. acc. after 3 days treatment wit h each of the DA agonists, SKF 38393 (4.0 mg/kg/day), R((+))-6-Bromo-A PB hydrobromide (4.0 mg/kg/day), or bromocriptine (5.0 mg/kg/day). Thu s, DA agonists mimick the effect of cocaine on the expression of MOR m RNA in n. acc. These data confirm the involvement of dopaminergic mech anisms in the mediation of cocaine effects, indicate the comparability of actions of indirect and direct DA agonists, and point to the usefu lness of cocaine as a tool to expose interaction between dopaminergic and opioid systems. The results suggest that activation of more than o ne type of DA receptor is required for the increased expression of MOR mRNA.