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Kappa opioid receptor activation decreases inhibitory transmission and antagonizes alcohol effects in rat central amygdala.
Neuropharmacology. 2014 Feb; 77:294-302.N

Abstract

Activation of the kappa opioid receptor (KOR) system mediates negative emotional states and considerable evidence suggests that KOR and their natural ligand, dynorphin, are involved in ethanol dependence and reward. The central amygdala (CeA) plays a major role in alcohol dependence and reinforcement. Dynorphin peptide and gene expression are activated in the amygdala during acute and chronic administration of alcohol, but the effects of activation or blockade of KOR on inhibitory transmission and ethanol effects have not been studied. We used the slice preparation to investigate the physiological role of KOR and interaction with ethanol on GABA(A) receptor-mediated synaptic transmission. Superfusion of dynorphin or U69593 onto CeA neurons decreased evoked inhibitory postsynaptic potentials (IPSPs) in a concentration-dependent manner, an effect prevented by the KOR antagonist norbinaltorphimine (norBNI). Applied alone, norBNI increased GABAergic transmission, revealing a tonic endogenous activity at KOR. Paired-pulse analysis suggested a presynaptic KOR mechanism. Superfusion of ethanol increased IPSPs and pretreatment with KOR agonists diminished the ethanol effect. Surprisingly, the ethanol-induced augmentation of IPSPs was completely obliterated by KOR blockade. Our results reveal an important role of the dynorphin/KOR system in the regulation of inhibitory transmission and mediation of ethanol effects in the CeA.

Authors+Show Affiliations

Department of Physiology, Louisiana State University, Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70130, USA.Committee on the Neurobiology of Addictive Disorders & Pearson Center for Alcoholism and Addiction Research, SP30 2400, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.Committee on the Neurobiology of Addictive Disorders & Pearson Center for Alcoholism and Addiction Research, SP30 2400, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.Committee on the Neurobiology of Addictive Disorders & Pearson Center for Alcoholism and Addiction Research, SP30 2400, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: pschweitzer@scripps.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24157490

Citation

Gilpin, Nicholas W., et al. "Kappa Opioid Receptor Activation Decreases Inhibitory Transmission and Antagonizes Alcohol Effects in Rat Central Amygdala." Neuropharmacology, vol. 77, 2014, pp. 294-302.
Gilpin NW, Roberto M, Koob GF, et al. Kappa opioid receptor activation decreases inhibitory transmission and antagonizes alcohol effects in rat central amygdala. Neuropharmacology. 2014;77:294-302.
Gilpin, N. W., Roberto, M., Koob, G. F., & Schweitzer, P. (2014). Kappa opioid receptor activation decreases inhibitory transmission and antagonizes alcohol effects in rat central amygdala. Neuropharmacology, 77, 294-302. https://doi.org/10.1016/j.neuropharm.2013.10.005
Gilpin NW, et al. Kappa Opioid Receptor Activation Decreases Inhibitory Transmission and Antagonizes Alcohol Effects in Rat Central Amygdala. Neuropharmacology. 2014;77:294-302. PubMed PMID: 24157490.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Kappa opioid receptor activation decreases inhibitory transmission and antagonizes alcohol effects in rat central amygdala. AU - Gilpin,Nicholas W, AU - Roberto,Marisa, AU - Koob,George F, AU - Schweitzer,Paul, Y1 - 2013/10/21/ PY - 2013/04/26/received PY - 2013/09/19/revised PY - 2013/10/08/accepted PY - 2013/10/26/entrez PY - 2013/10/26/pubmed PY - 2014/8/27/medline KW - Alcohol KW - Amygdala KW - GABA KW - Kappa KW - Opioid KW - Synaptic SP - 294 EP - 302 JF - Neuropharmacology JO - Neuropharmacology VL - 77 N2 - Activation of the kappa opioid receptor (KOR) system mediates negative emotional states and considerable evidence suggests that KOR and their natural ligand, dynorphin, are involved in ethanol dependence and reward. The central amygdala (CeA) plays a major role in alcohol dependence and reinforcement. Dynorphin peptide and gene expression are activated in the amygdala during acute and chronic administration of alcohol, but the effects of activation or blockade of KOR on inhibitory transmission and ethanol effects have not been studied. We used the slice preparation to investigate the physiological role of KOR and interaction with ethanol on GABA(A) receptor-mediated synaptic transmission. Superfusion of dynorphin or U69593 onto CeA neurons decreased evoked inhibitory postsynaptic potentials (IPSPs) in a concentration-dependent manner, an effect prevented by the KOR antagonist norbinaltorphimine (norBNI). Applied alone, norBNI increased GABAergic transmission, revealing a tonic endogenous activity at KOR. Paired-pulse analysis suggested a presynaptic KOR mechanism. Superfusion of ethanol increased IPSPs and pretreatment with KOR agonists diminished the ethanol effect. Surprisingly, the ethanol-induced augmentation of IPSPs was completely obliterated by KOR blockade. Our results reveal an important role of the dynorphin/KOR system in the regulation of inhibitory transmission and mediation of ethanol effects in the CeA. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/24157490/Kappa_opioid_receptor_activation_decreases_inhibitory_transmission_and_antagonizes_alcohol_effects_in_rat_central_amygdala_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(13)00479-6 DB - PRIME DP - Unbound Medicine ER -