TRANSIENT UP-REGULATION OF MU-OPIOID RECEPTOR MESSENGER-RNA LEVELS INNUCLEUS-ACCUMBENS DURING CHRONIC COCAINE ADMINISTRATION

Chronic continuous cocaine administration for 3 days has been shown to upregulate the level of mu opioid receptor (MOR) mRNA in the nucleus accumbens (n, acc.) of rat brain. Dopamine (DA) antagonists, SCH 23390 , eticlopride, and nafadotride, blocked, and DA agonists, SKF 38393, R (+)-6-bromo-APB hydrobromide, and bromocriptine, mimicked the cocaine- induced upregulation of MOR mRNA, suggesting involvement of both subfa milies of DA receptors in the effect of cocaine. In the present study the time course of cocaine-induced and DA agonist induced alterations in the level of MOR mRNA in n. acc, has been determined and compared w ith the changes in the level of MOR binding sites. Male Sprague-Dawley rats were treated with saline, cocaine (50 mg.kg(-1).day(-1)), or DA agonists for periods between 24 and 336 h. Expression of MOR mRNA in n . acc, was estimated using quantitative competitive polymerase chain r eaction assays following reverse transcription. The cocaine-induced up regulation of MOR mRNA in n. acc. was transient, developing 2 days aft er exposure, and peaking at 3 days with return to baseline levels by 4 days of chronic continuous cocaine treatment. The temporal characteri stics of DA agonist induced increase in the levels of MOR mRNA in n. a cc, were similar to those of cocaine, with maximum effect after 3 days of treatment. The density of [H-3]DAMGO binding sites in n. acc. was 30% higher after 3 days of cocaine administration than in saline-treat ed control animals, but returned toward baseline levels after 4 days o f cocaine treatment. No changes in the binding of [H-3]DAMGO were dete cted after 7 or 14 days exposure to cocaine. The affinity of [H-3]DAMG O to n. acc. membranes (similar to 2.0 nM) was unchanged during the co caine treatment.