The novel micro-opioid receptor antagonist, [N-allyl-Dmt(1)]endomorphin-2, attenuates the enhancement of GABAergic neurotransmission by ethanol.

Journal Article (Journal Article)

AIMS: We investigated the effects of [N-allyl-Dmt(1)]endomorphin-2 (TL-319), a novel and highly potent micro-opioid receptor antagonist, on ethanol (EtOH)-induced enhancement of GABA(A) receptor-mediated synaptic activity in the hippocampus. METHODS: Evoked and spontaneous inhibitory postsynaptic currents (eIPSCs and sIPSCs) were isolated from CA1 pyramidal cells from brain slices of male rats using whole-cell patch-clamp techniques. RESULTS: TL-319 had no effect on the baseline amplitude of eIPSCs or the frequency of sIPSCs. However, it induced a dose-dependent suppression of an ethanol-induced increase of sIPSC frequency with full reversal at concentrations of 500 nM and higher. The non-specific competitive opioid receptor antagonist naltrexone also suppressed EtOH-induced increases in sIPSC frequency but only at a concentration of 60 microM. CONCLUSION: These data indicate that blockade of micro-opioid receptors by low concentrations of [N-allyl-Dmt(1)]endomorphin-2 can reverse ethanol-induced increases in GABAergic neurotransmission and possibly alter its anxiolytic or sedative effects. This suggests the possibility that high potency opioid antagonists may emerge as possible candidate compounds for the treatment of ethanol addiction.

Full Text

Duke Authors

Cited Authors

  • Li, Q; Okada, Y; Marczak, E; Wilson, WA; Lazarus, LH; Swartzwelder, HS

Published Date

  • January 2009

Published In

Volume / Issue

  • 44 / 1

Start / End Page

  • 13 - 19

PubMed ID

  • 18971291

Pubmed Central ID

  • PMC2724860

Electronic International Standard Serial Number (EISSN)

  • 1464-3502

Digital Object Identifier (DOI)

  • 10.1093/alcalc/agn085


  • eng

Conference Location

  • England