title: Kappa opioid receptor activation decreases inhibitory transmission and antagonizes alcohol effects in rat central amygdala.
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.affiliation: Department of Physiology, Louisiana State University, Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70130, USA.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Gilpin
authors.affiliation: 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.
authors.forename: Marisa
authors.initials: M
authors.lastname: Roberto
authors.affiliation: 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.
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
authors.affiliation: 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.
authors.forename: Paul
authors.initials: P
authors.lastname: Schweitzer
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D044482:Benzeneacetamides / Q000494:pharmacology*; D004399:Dynorphins / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism
chemical_list: D044482:Benzeneacetamides; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D000431:Ethanol; D009271:Naltrexone; D004399:Dynorphins; C045444:U 69593
keywords: Alcohol; Amygdala; GABA; Kappa; Opioid; Synaptic