Effect of kappa-opioid receptor agonists U69593, U50488H, spiradoline and salvinorin A on cocaine-induced drug-seeking in rats

Aashish S. Morani, Bronwyn Kivell, Thomas E. Prisinzano, Susan Schenk

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


Our previous work indicated that pretreatment with the selective kappa-opioid receptor (KOPr) agonist, U69593, attenuated the ability of priming injections of cocaine to reinstate extinguished cocaine-seeking behavior. The present study expanded these initial tests to include other traditional KOPr agonists, U50488H, spiradoline (SPR), and salvinorin A (Sal A), an active constituent of the plant Salvia divinorum. Following acquisition and stabilization of cocaine self-administration, cocaine-produced drug-seeking was measured. This test was conducted in a single day and comprised an initial phase of self-administration, followed by a phase of extinguished responding. The final phase examined reinstatement of extinguished cocaine self-administration followed by a priming injection of cocaine (20.0 mg/kg, intraperitoneal (I.P.)) in combination with the various KOPr agonists. Cocaine-induced drug-seeking was attenuated by pretreatment with U69593 (0.3 mg/kg, subcutaneous (S.C.)), U50488H (30.0 mg/kg, I.P.), SPR (1.0, 3.0 mg/kg, I.P.) and Sal A (0.3, 1.0 mg/kg, I.P.). Sal A (0.3, 1.0 mg/kg, I.P.) had no effect on operant responding to obtain sucrose reinforcement or on cocaine-induced hyperactivity. These findings show that Sal A, like other traditional KOPr agonists attenuates cocaine-induced drug-seeking behavior.

Original languageEnglish
Pages (from-to)244-249
Number of pages6
JournalPharmacology Biochemistry and Behavior
Issue number2
StatePublished - Dec 2009

Bibliographical note

Funding Information:
This work was funded by Wellington Medical Research Foundation , The Neurological Foundation of New Zealand and grant DA018151 (T.E.P.) from the National Institute on Drug Abuse (NIDA) . The authors are thankful for the technical assistance of Mr. Alex Howard, Mr. Lincoln Hely and Mr. Richard Moore.


  • Cocaine self-administration
  • Drug-seeking
  • Kappa-opioid agonist
  • Salvinorin A
  • Spiradoline
  • U50488H
  • U69593

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience


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