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

Pharmacol Biochem Behav. 2009 Dec;94(2):244-9. doi: 10.1016/j.pbb.2009.09.002. Epub 2009 Sep 10.


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 (20.0mg/kg, intraperitoneal (I.P.)) in combination with the various KOPr agonists. Cocaine-induced drug-seeking was attenuated by pretreatment with U69593 (0.3mg/kg, subcutaneous (S.C.)), U50488H (30.0mg/kg, I.P.), SPR (1.0, 3.0mg/kg, I.P.) and Sal A (0.3, 1.0mg/kg, I.P.). Sal A (0.3, 1.0mg/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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / pharmacology
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / therapeutic use*
  • Animals
  • Behavior, Addictive / prevention & control
  • Behavior, Addictive / psychology
  • Benzeneacetamides / pharmacology
  • Benzeneacetamides / therapeutic use*
  • Cocaine / administration & dosage*
  • Diterpenes, Clerodane / pharmacology
  • Diterpenes, Clerodane / therapeutic use*
  • Male
  • Pyrrolidines / pharmacology
  • Pyrrolidines / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, kappa / agonists*
  • Receptors, Opioid, kappa / physiology
  • Self Administration


  • Benzeneacetamides
  • Diterpenes, Clerodane
  • Pyrrolidines
  • Receptors, Opioid, kappa
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Cocaine
  • U 69593
  • spiradoline
  • salvinorin A