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

Sari E Izenwasser, Jane B. Acri, Paul M. Kunko, Toni Shippenberg

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

U-69593, the selective κ-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 D1 and D2 receptors were measured using (3H]SCH 23390 or [3H]sulpiride, respectively, in caudate putamen and nucleus accumbens. Two days after the last of three injections, dopamine D2 receptors in the caudate putamen were decreased by approximately 40%, with no change in D1 receptors. Dopamine D2 receptor number had returned to normal by 10 days posttreatment. In contrast, in the nucleus accumbens there was a small, nonsignificant decrease in dopamine D2 receptors 2 days after treatment, but a large increase (65%) after 10 days. In agreement with the changes in D2 receptors, there was a significant downward shift in the locomotor activity curve for the D2 agonist quinpirole after a 2-day withdrawal. There were no differences in either the total amount of dopamine taken up or in the IC50 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 κ-opioid agonist induces long- term alterations in dopamine D2 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.

Original languageEnglish
Pages (from-to)275-283
Number of pages9
JournalSynapse
Volume30
Issue number3
DOIs
StatePublished - Nov 1 1998

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Dopamine D2 Receptors
Opioid Analgesics
Putamen
Nucleus Accumbens
Injections
Dopamine
Quinpirole
Therapeutics
Dopamine D1 Receptors
Sulpiride
Dopamine Plasma Membrane Transport Proteins
Caudate Nucleus
Presynaptic Terminals
Locomotion
Cocaine
Inhibitory Concentration 50
Sprague Dawley Rats
U 69593

Keywords

  • Cocaine
  • Sensitization
  • Tolerance

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology

Cite this

Repeated treatment with the selective Kappa opioid agonist U-69593 produces a marked depletion of dopamine D2 receptors. / Izenwasser, Sari E; Acri, Jane B.; Kunko, Paul M.; Shippenberg, Toni.

In: Synapse, Vol. 30, No. 3, 01.11.1998, p. 275-283.

Research output: Contribution to journalArticle

Izenwasser, Sari E ; Acri, Jane B. ; Kunko, Paul M. ; Shippenberg, Toni. / Repeated treatment with the selective Kappa opioid agonist U-69593 produces a marked depletion of dopamine D2 receptors. In: Synapse. 1998 ; Vol. 30, No. 3. pp. 275-283.
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