Supersensitive Kappa Opioid Receptors Promotes Ethanol Withdrawal-Related Behaviors and Reduce Dopamine Signaling in the Nucleus Accumbens

@article{Rose2016SupersensitiveKO,
  title={Supersensitive Kappa Opioid Receptors Promotes Ethanol Withdrawal-Related Behaviors and Reduce Dopamine Signaling in the Nucleus Accumbens},
  author={J. Rose and Anushree N Karkhanis and Rong Chen and D. Gioia and M. L{\'o}pez and H. Becker and B. McCool and Sara R. Jones},
  journal={International Journal of Neuropsychopharmacology},
  year={2016},
  volume={19}
}
Background: Chronic ethanol exposure reduces dopamine transmission in the nucleus accumbens, which may contribute to the negative affective symptoms associated with ethanol withdrawal. Kappa opioid receptors have been implicated in withdrawal-induced excessive drinking and anxiety-like behaviors and are known to inhibit dopamine release in the nucleus accumbens. The effects of chronic ethanol exposure on kappa opioid receptor-mediated changes in dopamine transmission at the level of the… Expand
Switch from excitatory to inhibitory actions of ethanol on dopamine levels after chronic exposure: Role of kappa opioid receptors
TLDR
Findings indicate that augmentation of dynorphin/KOR system activity drives the reduction in stimulated (electrical and ethanol) dopamine release in the NAc, and blockade of KORs is a promising avenue for developing pharmacotherapies for alcoholism. Expand
Distinct Effects of Nalmefene on Dopamine Uptake Rates and Kappa Opioid Receptor Activity in the Nucleus Accumbens Following Chronic Intermittent Ethanol Exposure
TLDR
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 / dynorphin system alters stress and threat responding during acute withdrawal from intermittent alcohol drinking in male mice.
TLDR
BNST dynorphin recruitment during acute withdrawal is confirmed as playing a key role in altered behavioral responses to stressful stimuli, and knockdown of dynorph in the BNST using a viral shRNA affected swim stress behavior and responses to TMT in alcohol drinkers and controls, but did not affect alcohol drinking. Expand
The selective κ-opioid receptor antagonist JDTic attenuates the alcohol deprivation effect in rats
TLDR
Results suggest that nucleus accumbens shell λ-opioidergic mechanisms may have a role in mediating relapse to ethanol intake and that κ-antagonism could be a valuable adjunct in ethanol relapse prevention. Expand
Kappa-opioid receptor-dependent changes in dopamine and anxiety-like or approach-avoidance behavior occur differentially across the nucleus accumbens shell rostro-caudal axis
TLDR
Results indicate that there is heterogeneity across the rostro-caudal axis of the NAc shell in the effects of KOR stimulation on affective behaviors, and suggest that this might be due to differences in KOR control over dopamine release. Expand
Dynorphin/Kappa Opioid Receptor Signaling in Preclinical Models of Alcohol, Drug, and Food Addiction.
TLDR
This chapter will delve into the mechanisms by which modulation of the dynorphin/KOR system may be therapeutic, examining the effects of chronic ethanol exposure on KOR function and the downstream effects on dopamine transmission. Expand
Adolescent Intermittent Ethanol Exposure Effects on Kappa Opioid Receptor Mediated Dopamine Transmission: Sex and Age of Exposure Matter
TLDR
The data suggest that AIE exposure impact on neural processes is dependent on sex and exposure timing, and changes in KOR function following AIE Exposure are shown, the first study to show changes in kappa opioid receptor function followingAIE exposure. Expand
Kappa-opioid receptor-dependent changes in dopamine and affective behavior occur differentially across the nucleus accumbens shell rostro-caudal axis
TLDR
Results indicate that there is heterogeneity across the rostro-caudal axis of the NAc shell in the effects of KOR stimulation on affective behaviors, and suggest that this might be due to differences in KOR control over dopamine release. Expand
Adolescent intermittent ethanol exposure effects on kappa opioid receptor mediated dopamine transmission: Sex and age of exposure matter
TLDR
Data suggest that AIE-exposure impact on neural processes is dependent on sex and exposure timing, and changes in KOR function following AIE exposure are shown, the first study to show changes in kappa opioid receptor function followingAIE exposure. Expand
Kappa-opioid receptor stimulation in the nucleus accumbens shell: Differential effects across the rostro-caudal axis on dopamine transmission and affective behavior
Neural activity in the nucleus accumbens (NAc) shell has long been implicated in the regulation of negative and positive affect. Classically, the dynorphin/kappa opioid receptor (KOR) system in theExpand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 65 REFERENCES
Endogenous kappa opioid receptor systems modulate the responsiveness of mesoaccumbal dopamine neurons to ethanol.
TLDR
It is demonstrated that inhibition of KOPR leads to increased sensitivity to the DA-releasing effects of ethanol in the nucleus accumbens, and this effect is observed in mice repeatedly exposed to ethanol. Expand
Voluntary Ethanol Intake Predicts κ-Opioid Receptor Supersensitivity and Regionally Distinct Dopaminergic Adaptations in Macaques
TLDR
The strong relationship between KOR activity and voluntary ethanol intake observed here gives further support to the hypothesis that KORs may provide a promising pharmacotherapeutic target in the treatment of alcoholism. Expand
Blockade of kappa opioid receptors attenuates the development of depressive-like behaviors induced by cocaine withdrawal in rats
TLDR
It is suggested that blockade of KORs before exposure to a stressor (in this case, cocaine withdrawal or forced swimming) can attenuate the development of stress-induced behavioral adaptations. Expand
κ-opioid receptors are implicated in the increased potency of intra-accumbens nalmefene in ethanol-dependent rats
TLDR
The concept that dysregulation of DYN/κ-opioid receptor systems contributes to the excessive self-administration observed in dependent animals is supported and pharmacotherapeutics for ethanol dependence that target κ-opIOid receptors are suggested to be preferable to those that target μ- and δ-opiaid receptor mechanisms alone. Expand
Pharmacological evidence for a motivational role of kappa-opioid systems in ethanol dependence.
  • B. Walker, G. Koob
  • Medicine
  • Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
  • 2008
TLDR
The results with nor-BNI confirm that kappa-opioid receptor antagonism selectively decreases dependence-induced ethanol self-administration, which supports the hypothesis that dynorphin/kappa-OPioid systems are dysregulated in dependence and contribute to the increased drinking seen during acute withdrawal in dependent rats. Expand
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
Lack of stimulant and anxiolytic-like effects of ethanol and accelerated development of ethanol dependence in mu-opioid receptor knockout mice
TLDR
The results implicate MOR in affective and somatic aspects of ethanol exposure and withdrawal and support the hypothesis that the clinical efficacy of the opioid receptor antagonist naltrexone against relapse to alcoholism might be related to an action on the acute positive effects of alcohol rather than the negative affect of abstinence. Expand
Effects of kappa-opioid receptor ligands on intracranial self-stimulation in rats.
TLDR
These data provide further evidence that stimulation of brain kappa-receptors may trigger certain depressive-like signs, and that kappa antagonists may have efficacy as antidepressants without having reward-related actions of their own. Expand
The One-Two Punch of Alcoholism: Role of Central Amygdala Dynorphins/Kappa-Opioid Receptors
TLDR
Increased DYN A and increased KOR signaling could set the stage for a one-two punch during withdrawal that drives excessive alcohol consumption in alcohol dependence. Expand
Ethanol withdrawal enhances the prodynorphin system activity in the rat nucleus accumbens
TLDR
The data indicate that after 48 h of ethanol withdrawal, prodynorphin neurons are highly activated, and the increased supply of endogenous kappa opioid receptor agonists in the nucleus accumbens at that time may promote aversive states during ethanol withdrawal. Expand
...
1
2
3
4
5
...