U69593, a kappa-opioid agonist, decreases cocaine self-administration and decreases cocaine-produced drug-seeking

  title={U69593, a kappa-opioid agonist, decreases cocaine self-administration and decreases cocaine-produced drug-seeking},
  author={Susan Schenk and Brian Partridge and Toni Shaun Shippenberg},
Abstract  Rationale: Previous research has shown that kappa-opioid receptor agonists decrease intravenous cocaine self-administration. These agents also block the development of sensitization that occurs following repeated exposure to cocaine, which is thought to be important in the maintenance and reinstatement of compulsive drug-seeking behavior. Objectives: This study was designed to determine the effects of the kappa-opioid receptor agonist, U69593, on the maintenance of cocaine self… 

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

Effects of Mixed-Action κ/μ Opioids on Cocaine Self-Administration and Cocaine Discrimination by Rhesus Monkeys

Mixed κ/μ agonists appear to offer some advantages over selective κ agonists as potential treatments for cocaine abuse and may reduce cocaine self-administration without altering cocaine's discriminative stimulus effects.

Inhibition of kappa opioid receptors attenuated increased cocaine intake in rats with extended access to cocaine

The data suggest that increased motivation for cocaine in rats with extended access may be related to increased κ opioid activity and may contribute to compulsive use.

Reinstatement of extinguished drug-taking behavior in rats: effect of the kappa-opioid receptor agonist, U69593

The failure of U69593 to attenuate GBR 12909- or WIN 35,428-produced cocaine seeking suggests that the effect of this kappa-opioid receptor agonist on cocaine seeking is not mediated by interactions at the dopamine transporter.

Enadoline and butorphanol: evaluation of kappa-agonists on cocaine pharmacodynamics and cocaine self-administration in humans.

The data suggest that these kappa-agonists may be safely administered in the presence of cocaine but do not produce significant attenuation of cocaine's direct effects or self-administration under these acute dosing conditions.

U-69593, a kappa opioid receptor agonist, decreases cocaine-induced behavioral sensitization in female rats.

Repeated exposure to U-69593 (0.32 mg/kg) prior to cocaine decreased the development of behavioral sensitization in OVX-EB-implanted rats, indicating that the KOPr system participates in estradiol modulation of cocaine-induced behavioral sensitized in the female rat.

A single, extinction-based treatment with a kappa opioid receptor agonist elicits a long-term reduction in cocaine relapse

Data suggest U50 elicits its long-term anti-relapse effects through a KOR-p38 MAPK-specific aversive counterconditioning of the operant cocaine-seeking response, and warrants further consideration of the therapeutic potential of KOR agonists in the treatment of addiction.



Effects of kappa opioids on cocaine self-administration by rhesus monkeys.

It is shown that chronic administration of EKC and U50,588 produce a dose-dependent, kappa receptor-mediated and often sustained decrease in cocaine self-administration, which may complicate their use as treatments for cocaine dependence.

Development of behavioral sensitization to cocaine: influence of kappa opioid receptor agonists.

It is demonstrated that the repeated activation of kappa opioid receptors prevents the locomotor activation that occurs in response to an acute cocaine challenge as well as the sensitized motor responses that develop after the repeated administration of cocaine.

Effects of kappa opioid agonists on cocaine- and food-maintained responding by rhesus monkeys.

  • N. MelloS. Negus
  • Biology, Medicine
    The Journal of pharmacology and experimental therapeutics
  • 1998
It is suggested that kappa opioid agonists may be a useful approach to the development of new pharmacological treatments for cocaine dependence and undesirable side effects may limit their clinical usefulness.

kappa-Opioid receptor agonists prevent sensitization to the conditioned rewarding effects of cocaine.

It is demonstrated that sensitization develops to the conditioned rewarding effects of cocaine and that the activation of central nervous system kappa-opioid receptors prevents the development of this phenomenon.

Modulation of the discriminative stimulus effects of cocaine by mu and kappa opioids.

The effects of cocaine alone and after pretreatment with selective mu and kappa opioids were determined in squirrel monkeys trained to discriminate, indicating that the observed interactions were not simply the result of additive discriminative stimulus effects.

Increased responsiveness of mesolimbic and mesostriatal dopamine neurons to cocaine following repeated administration of a selective κ‐opioid receptor agonist

The findings indicate that the behavioral interactions of κ‐agonists with cocaine observed in this and previous studies cannot be attributed to a presynaptic inhibition of DA release and suggest that postsynaptic or non‐DA mechanisms mediate the interaction of these agents with cocaine.

Reinstatement of extinguished cocaine-taking behavior by cocaine and caffeine