Repeated treatment with the selective kappa opioid agonist U-69593 produces a marked depletion of dopamine D2 receptors

✍ Scribed by Sari Izenwasser; Jane B. Acri; Paul M. Kunko; Toni Shippenberg

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 112 KB
• Volume: 30
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/(sici)1098-2396(199811)30:3<275::aid-syn5>3.0.co;2-8

✦ Synopsis

U-69593, the selective -opioid agonist, was repeatedly administered in single daily injections (0.32 mg/kg) to male, Sprague-Dawley rats. Two or ten days later, the rats were euthanized and dopamine D 1 and D 2 receptors were measured using ( 3 H]SCH 23390 or [ 3 H]sulpiride, respectively, in caudate putamen and nucleus accumbens. Two days after the last of three injections, dopamine D 2 receptors in the caudate putamen were decreased by approximately 40%, with no change in D 1 receptors. Dopamine D 2 receptor number had returned to normal by 10 days posttreatment. In contrast, in the nucleus accumbens there was a small, nonsignificant decrease in dopamine D 2 receptors 2 days after treatment, but a large increase (65%) after 10 days. In agreement with the changes in D 2 receptors, there was a significant downward shift in the locomotor activity curve for the D 2 agonist quinpirole after a 2-day withdrawal. There were no differences in either the total amount of dopamine taken up or in the IC 50 for cocaine to inhibit dopamine uptake following this treatment, suggesting that the dopamine transporter and presynaptic terminals were intact. The results of these studies demonstrate that repeated administration of a selective -opioid agonist induces long-term alterations in dopamine D 2 receptors. Furthermore, the finding that these changes in receptor number require both repeated injections and a withdrawal time greater than 1 day suggests that these alterations are compensatory in nature.