Corpus ID: 38393576

Pharmacological evidence for a motivational role of kappa-opioid systems in ethanol dependence.

  title={Pharmacological evidence for a motivational role of kappa-opioid systems in ethanol dependence.},
  author={B. Walker and G. Koob},
  journal={Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology},
  volume={33 3},
  • B. Walker, G. Koob
  • Published 2008
  • Medicine
  • Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
The purpose of this study was to test the hypothesis that activation of the dynorphin/kappa (kappa)-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… Expand
The kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI), decreases morphine withdrawal and the consequent conditioned place aversion in rats
The data indicate that the binding of dynorphin-like peptides to KORs during opioid withdrawal serves to enhance withdrawal and its aversive consequences and suggest that selective KOR antagonists may be useful in reducing these aversive effects and consequent relapse. Expand
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. Expand
Effects of CRF1-receptor and opioid-receptor antagonists on dependence-induced increases in alcohol drinking by alcohol-preferring (P) rats.
These results confirm a role for brain CRF(1)-receptor systems in dependence-induced changes in the reinforcing properties of alcohol, and CRF-receptor blockade appears to suppress dependence- induced drinking at lower doses in P rats relative to other rat lines. Expand
alpha1-noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol.
The results suggest the involvement of the noradrenergic system in the excessive alcohol drinking seen during acute withdrawal in ethanol-dependent rats, which is consistent with the effect of anxiolytics on ethanol self-administration in nondependent animals. Expand
Blockade of ethanol reward by the kappa opioid receptor agonist U50,488H.
Low, nonaversive doses of the KOR agonist U50,488H blocked the rewarding properties of ethanol during conditioning, thus impairing the acquisition of conditioned place preference and indicating that the K OR/dynorphin system may acutely regulate ethanol intake via inhibition of the rewarding Properties of ethanol. Expand
Distinct Effects of Nalmefene on Dopamine Uptake Rates and Kappa Opioid Receptor Activity in the Nucleus Accumbens Following Chronic Intermittent Ethanol Exposure
Nalmefene attenuated dopamine uptake rates to a greater extent in brain slices from CIE-exposed mice, suggesting that dopamine transporter-KOR interactions may be fundamentally altered following CIE, and may attenuate withdrawal-induced increases in ethanol consumption by modulation of dopamine transmission through KORs. Expand
Activation of the kappa opioid receptor in the dorsal raphe nucleus mediates the aversive effects of stress and reinstates drug seeking
The results suggest that the adverse effects of stress may converge on the serotonergic system and offers an approach to controlling stress-induced dysphoria and relapse. Expand
Role of κ-Opioid Receptors in the Bed Nucleus of Stria Terminalis in Reinstatement of Alcohol Seeking
The data indicate that the BNST is a critical site for U50,488-induced reinstatement of alcohol seeking and suggest that KOR/dynorphin mechanisms in this brain area play a key role in stress-induced alcohol seeking. Expand
Supersensitive Kappa Opioid Receptors Promotes Ethanol Withdrawal-Related Behaviors and Reduce Dopamine Signaling in the Nucleus Accumbens
It is suggested that the chronic intermittent ethanol-induced increase in ethanol intake and anxiety/compulsive-like behaviors may be driven by greater kappa opioid receptor sensitivity and a hypodopaminergic state of the nucleus accumbens. Expand
Locus Coeruleus Kappa-Opioid Receptors Modulate Reinstatement of Cocaine Place Preference Through a Noradrenergic Mechanism
A previously unknown interaction between KORs and NA systems is identified and a NA regulation of K OR-dependent reinstatement of cocaine CPP is suggested, suggesting that adrenergic receptor interactions occur at KOR-expressing regions external to the LC. Expand