Pharmacological Evidence for a Motivational Role of κ-Opioid Systems in Ethanol Dependence

  title={Pharmacological Evidence for a Motivational Role of $\kappa$-Opioid Systems in Ethanol Dependence},
  author={Brendan M Walker and George F. Koob},
  • B. WalkerG. Koob
  • Published 1 February 2008
  • Medicine, Biology
  • Neuropsychopharmacology
The purpose of this study was to test the hypothesis that activation of the dynorphin/kappa (κ)-opioid system has a role in the increased consumption of ethanol in dependent animals. The effects of three opioid receptor antagonists with different effects on opioid receptors, naltrexone, nalmefene, and nor-binaltorphimine (nor-BNI), were compared in their ability to decrease ethanol self-administration in nondependent and ethanol-dependent male Wistar rats. Nalmefene and naltrexone are both… 

nor-BNI Antagonism of Kappa Opioid Agonist-Induced Reinstatement of Ethanol-Seeking Behavior

Results suggest that activation of KORs is a key mechanism in the regulation of ethanol-seeking behavior, but U50,488-induced reinstatement may not be fully selective for K ORs.

Involvement of dynorphin and kappa opioid receptor in yohimbine‐induced reinstatement of heroin seeking in rats

The present experiments suggest that the stress responsive ppDyn/KOP-r system is a critical component of the neural circuitry underlying the effect of yohimbine stress on heroin seeking behavior and HPA activity.

Species differences in the effects of the κ-opioid receptor antagonist zyklophin.

The κ-opioid receptor antagonist JDTic decreases ethanol intake in alcohol-preferring AA rats

It is suggested that κ-opioid receptor antagonists may be a valuable adjunct in the pharmacotherapy of ethanol use disorders and that accumbal λ-opIOid receptors participate in the modulation of the reinforcing effects of ethanol.

Blockade of ethanol reward by the kappa opioid receptor agonist U50,488H.




Kappa-opioid receptors and relapse-like drinking in long-term ethanol-experienced rats

Stimulation of κ-opioid receptors can increase ethanol intake, at least in long-term ethanol-experienced rats, and the nor-BNI experiments indicate that endogenous λ-OPioid receptor stimulation does not seem to be involved in relapse-like drinking after protracted abstinence.

Central Opioid Receptors Differentially Regulate the Nalmefene-Induced Suppression of Ethanol- and Saccharin-Reinforced Behaviors in Alcohol-Preferring (P) Rats

Evidence is provided that nalmefene suppresses EtOH-motivated behaviors via blockade of opioid receptors within the NACC and VTA, and under various dose conditions both reinforcer and neuroanatomical specificity can be observed.

Animal models of motivation for drinking in rodents with a focus on opioid receptor neuropharmacology.

  • G. KoobA. Roberts F. Weiss
  • Biology
    Recent developments in alcoholism : an official publication of the American Medical Society on Alcoholism, the Research Society on Alcoholism, and the National Council on Alcoholism
  • 2003
The apparently critical role of the mu receptor in ethanol reinforcement refocuses the neuropharmacology of ethanol reinforcement in the opioid peptide domain and opens a novel avenue for exploring medications for treating alcoholism.

Antidepressant-Like Effects of κ-Opioid Receptor Antagonists in the Forced Swim Test in Rats

Findings are consistent with the hypothesis that CREB-mediated induction of dynorphin in the NAc “triggers” immobility behavior in the FST and raise the possibility that κ-antagonists may have efficacy as antidepressants, but lack stimulant or reward-related effects.

Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats.

Findings are consistent with the hypothesis that CREB-mediated induction of dynorphin in the NAc "triggers" immobility behavior in the FST and raise the possibility that kappa-antagonists may have efficacy as antidepressants, but lack stimulant or reward-related effects.

Kappa-opioid receptor-mediated antinociception in the rat. II. Supraspinal in addition to spinal sites of action.

Analysis of antinociception induced by kappa- and mu-opioids was unaffected by systemic quaternary naltrexone revealing that it is mediated in the central nervous system, and suggests sites of action in brain in addition to spinal cord for both mu- and kappa -opioid receptor agonists.

κ Opioid Receptor Antagonism and Prodynorphin Gene Disruption Block Stress-Induced Behavioral Responses

The findings suggest that chronic swim stress may activate the κ opioid system to produce analgesia, immobility, and potentiation of the acute rewarding properties of cocaine in C57Bl/6 mice.

Involvement of μ-opioid receptors in alcohol drinking by alcohol-preferring AA rats

  • P. Hyytiä
  • Medicine, Biology
    Pharmacology Biochemistry and Behavior
  • 1993