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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.

journal_name

Neuropharmacology

journal_title

Neuropharmacology

authors

Gilpin NW,Roberto M,Koob GF,Schweitzer P

doi

10.1016/j.neuropharm.2013.10.005

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

294-302

eissn

0028-3908

issn

1873-7064

pii

S0028-3908(13)00479-6

journal_volume

77

pub_type

杂志文章

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