Endogenous kappa-opioid systems in opiate withdrawal: role in aversion and accompanying changes in mesolimbic dopamine release

Psychopharmacology (Berl). 1994 Jun;115(1-2):121-7. doi: 10.1007/BF02244761.

Abstract

The kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI) was recently shown to potentiate certain overt withdrawal signs in morphine-dependent rats. The present study sought to further assess this phenomenon by examining the influence of nor-BNI treatment upon the conditioned place aversion associated with the naloxone-precipitated withdrawal syndrome. In addition, in vivo microdialysis studies were conducted in morphine-dependent rats to determine whether nor-BNI treatment can modify withdrawal-induced changes in basal dopamine (DA) release within the mesolimbic system. Rats were pretreated with either saline or a single dose of nor-BNI and then received ascending doses of morphine for 10 days. A withdrawal syndrome was then precipitated by the administration of naloxone (1 mg/kg SC). In rats which received chronic morphine injections, administration of naloxone produced a characteristic withdrawal syndrome and a marked aversion for an environment previously associated with naloxone-precipitated withdrawal. Nor-BNI treatment potentiated most overt signs of physical dependence. This treatment also resulted in a greater withdrawal-induced place aversion. Morphine-dependent rats exhibited a marked reduction in basal mesolimbic DA release. An even greater decrease in basal DA release was observed in nor-BNI treated rats. These results suggest that endogenous kappa-systems are important in the modulation of mesolimbic DA release and the accompanying place aversion which occurs during opiate withdrawal.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Biogenic Monoamines / metabolism
  • Conditioning, Operant / drug effects
  • Dopamine / metabolism*
  • Injections, Intraventricular
  • Limbic System / metabolism*
  • Male
  • Microdialysis
  • Morphine Dependence / metabolism*
  • Morphine Dependence / psychology*
  • Naloxone / pharmacology
  • Naltrexone / administration & dosage
  • Naltrexone / analogs & derivatives
  • Naltrexone / pharmacology
  • Nucleus Accumbens / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, kappa / physiology*
  • Reinforcement, Psychology
  • Substance Withdrawal Syndrome / metabolism*
  • Substance Withdrawal Syndrome / psychology*

Substances

  • Biogenic Monoamines
  • Receptors, Opioid, kappa
  • Naloxone
  • norbinaltorphimine
  • Naltrexone
  • Dopamine