The kappa-opioid receptor agonist U-69593 attenuates cocaine-induced behavioral sensitization in the rat

Brain Res. 1993 Jul 9;616(1-2):335-8. doi: 10.1016/0006-8993(93)90228-f.


The effects of treatment with the selective kappa-opioid receptor agonist U-69593 upon cocaine-induced changes in locomotor activity and stereotypy were examined in rats. U-69593 (0.16 mg/kg s.c.) administered either acutely or chronically attenuated both the motor stimulant effect and stereotypy produced by an acute injection of cocaine (20 mg/kg i.p.). Daily cocaine treatment resulted in sensitization to both effects of cocaine. In contrast, no such sensitized responses were seen in animals which had received U-69593 either prior to or in conjunction with daily cocaine treatment. These data demonstrate that activation of kappa-opioid receptors attenuates the acute and chronic effects of cocaine on locomotor activity and stereotypy. Given the inhibitory effects ascribed to both exogenous and endogenous kappa-opioid agonists upon dopamine release in the mesolimbic dopaminergic system, it is suggested that this action may underlie the observed effects of U-69593 on cocaine-induced changes in locomotor activity and stereotypy.

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Benzeneacetamides*
  • Cocaine / antagonists & inhibitors
  • Cocaine / pharmacology*
  • Drug Administration Schedule
  • Male
  • Motor Activity / drug effects*
  • Pyrrolidines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, kappa / drug effects
  • Receptors, Opioid, kappa / physiology*
  • Reference Values
  • Stereotyped Behavior / drug effects*
  • Time Factors


  • Analgesics
  • Benzeneacetamides
  • Pyrrolidines
  • Receptors, Opioid, kappa
  • Cocaine
  • U 69593