κ-opioid receptors are implicated in the increased potency of intra-accumbens nalmefene in ethanol-dependent rats

@article{Nealey2011opioidRA,
  title={$\kappa$-opioid receptors are implicated in the increased potency of intra-accumbens nalmefene in ethanol-dependent rats},
  author={Kathryn A. Nealey and Alexander W. Smith and Seth M Davis and Daniel G. Smith and Brendan M Walker},
  journal={Neuropharmacology},
  year={2011},
  volume={61},
  pages={35-42}
}
Previously, it was shown that ethanol-dependent animals display increased sensitivity to the general opioid receptor antagonist nalmefene compared to naltrexone. It was hypothesized that the dissociable effects of the two antagonists were attributable to a κ-opioid receptor mechanism. Nucleus accumbens dynorphin is upregulated following chronic ethanol exposure and such neuroadaptations could contribute to nalmefene's increased potency in ethanol-dependent animals. To test this hypothesis, male… Expand
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References

SHOWING 1-10 OF 64 REFERENCES
Pharmacological Evidence for a Motivational Role of κ-Opioid Systems in Ethanol Dependence
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 ofExpand
Central Opioid Receptors Differentially Regulate the Nalmefene-Induced Suppression of Ethanol- and Saccharin-Reinforced Behaviors in Alcohol-Preferring (P) Rats
TLDR
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. Expand
Suppression of ethanol responding by centrally administered CTOP and naltrindole in AA and Wistar rats.
TLDR
Results confirm previous results which showed that both mu- and delta-opioid receptors are involved in the regulation of ethanol self-administration and indicate that genetic differences between AA and Wistar rats produced by selection do not modify the effects of opioid antagonists. Expand
Ethanol alters the effect of kappa receptor ligands on dopamine release in the nucleus accumbens
TLDR
A change in responsiveness of dopamine neurons following repeated ethanol administration could be related to changes in the sensitivity of kappa-receptor systems and/or an increase in dynorphin tone in the nucleus accumbens. Expand
κ-Opioid receptor modulation of accumbal dopamine concentration during operant ethanol self-administration
TLDR
The altered dopamine response to NOR-BNI during ethanol drinking suggests that KOPr blockade temporarily uncovered a pharmacological stimulation of dopamine release by ethanol, suggesting that the K OPr is not involved in ethanol-reinforced behavior under the limited conditions the authors studied. Expand
A single injection of the kappa opioid antagonist norbinaltorphimine increases ethanol consumption in rats
RationaleKappa opioid receptor (KOR) agonists interfere with the reinforcing effects of drugs of abuse. KOR agonists decrease heroin, cocaine, and ethanol self-administration, and block heroin andExpand
Antidepressant-Like Effects of κ-Opioid Receptor Antagonists in the Forced Swim Test in Rats
We showed previously that cAMP response element-binding protein (CREB) within the nucleus accumbens (NAc) of rats regulates immobility in the forced swim test (FST), an assay used to studyExpand
Activation of the kappa opioid receptor in the dorsal raphe nucleus mediates the aversive effects of stress and reinstates drug seeking
TLDR
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
A comparison of the effects of the opioid antagonists naltrexone, naltrindole, and beta-funaltrexamine on ethanol consumption in the rat.
TLDR
The data suggest that ethanol consumption using the limited access paradigm in the outbred rat is modulated by mu rather than delta-opioid receptors, which is not consistent with other data showing that delta antagonists decrease ethanol consumption. Expand
Effects of κ-opioid receptor ligands on intracranial self-stimulation in rats
TLDR
These data provide further evidence that stimulation of brain κ-receptors may trigger certain depressive-like signs, and that κ antagonists may have efficacy as antidepressants without having reward-related actions of their own. Expand
...
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