Kappa opioid inhibition of morphine and cocaine self-administration in rats

Brain Res. 1995 May 29;681(1-2):147-52. doi: 10.1016/0006-8993(95)00306-b.


Two kappa agonists, U50,488 and spiradoline, produced dose-related acute decreases in both morphine and cocaine self-administration in rats; higher doses of both agents were required to decrease rates of bar-pressing for water. On the day after kappa agonist administration, both agents produced extinction-like patterns of responding in many rats self-administering morphine or cocaine but not in rats responding for water. Two days after their administration, both U50,488 and spiradoline produced significant decreases in both morphine and cocaine intake; some rats continued to show decreases in drug self-administration for 5-6 days. Although the kappa antagonist nor-binaltorphimine (10 mg/kg s.c.) had no effect itself on either morphine or cocaine self-administration, it fully antagonized the effects of U50,488 (10 m/kg i.p.). The results suggest that although endogenous kappa opioid systems may not tonically modulate mechanisms involved in drug reinforcement, pharmacological activation of kappa pathways may be a novel and effective pharmacological approach to treating both opioid and stimulant addiction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Analgesics / pharmacology
  • Animals
  • Cocaine / administration & dosage
  • Cocaine / pharmacology*
  • Dose-Response Relationship, Drug
  • Extinction, Psychological / drug effects
  • Female
  • Morphine / administration & dosage
  • Morphine / pharmacology*
  • Naltrexone / analogs & derivatives
  • Naltrexone / pharmacology
  • Narcotics / administration & dosage
  • Narcotics / pharmacology*
  • Pyrrolidines / antagonists & inhibitors
  • Pyrrolidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, kappa / agonists*
  • Reinforcement, Psychology
  • Self Administration


  • Analgesics
  • Narcotics
  • Pyrrolidines
  • Receptors, Opioid, kappa
  • norbinaltorphimine
  • Naltrexone
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Morphine
  • Cocaine
  • spiradoline