κ-Opioid receptors in the central amygdala regulate ethanol actions at presynaptic GABAergic sites.

Published

Journal Article

Human and animal studies indicate that κ-opioid receptors (KORs) are involved in ethanol drinking and dependence (Xuei et al., 2006; Walker and Koob, 2008; Walker et al., 2011). Using in vitro single-cell recording techniques in mouse brain slices, we examined the physiologic effects of KOR activation in the central amygdala (CeA) on GABAergic neurotransmission and its interaction with acute ethanol. A selective KOR agonist (U69593, 1 μM) diminished evoked GABAergic inhibitory postsynaptic currents (IPSCs) by 18% (n = 10), whereas blockade of KORs with a selective antagonist (nor-binaltorphimine, 1 μM) augmented the baseline evoked GABAergic IPSCs by 14% (P < 0.01; n = 34), suggesting that the KOR system contributes to tonic inhibition of GABAergic neurotransmission in the CeA. In addition, the enhancement by acute ethanol of GABAergic IPSC amplitudes was further augmented by pharmacologic blockade of KORs, from 14% (n = 36) to 27% (n = 26; P < 0.01), or by genetic deletion of KORs, from 14% in wild-type mice (n = 19) to 34% in KOR knockout mice (n = 13; P < 0.01). Subsequent experiments using tetrodotoxin to block activity-dependent neurotransmission suggest that KORs regulate GABA release at presynaptic sites. Our data support the idea that KORs modulate GABAergic synaptic responses and ethanol effects as one of multiple opioid system-dependent actions of ethanol in the CeA, possibly in a circuit-specific manner.

Full Text

Duke Authors

Cited Authors

  • Kang-Park, M; Kieffer, BL; Roberts, AJ; Siggins, GR; Moore, SD

Published Date

  • July 2013

Published In

Volume / Issue

  • 346 / 1

Start / End Page

  • 130 - 137

PubMed ID

  • 23587526

Pubmed Central ID

  • 23587526

Electronic International Standard Serial Number (EISSN)

  • 1521-0103

Digital Object Identifier (DOI)

  • 10.1124/jpet.112.202903

Language

  • eng

Conference Location

  • United States