We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The Novel μ-Opioid Receptor Antagonist, [N-Allyl-Dmt[sup1]]Endomorphin-2, Attenuates the Enhancement of GABAergic Neurotransmission by Ethanol.
- Authors
Qiang Li; Okada, Yoshio; Marczak, Ewa; Wilson, Wilkie A.; Lazarus, Lawrence H.; Swartzwelder, H. S.
- Abstract
Abstract Aims: We investigated the effects of [N-allyl-Dmt[sup1]]endomorphin-2 (TL-3 19), a novel and highly potent μ-opioid receptor antagonist, on ethanol (EtOH)-induced enhancement of GABA[subA] receptor-mediated synaptic activity in the hippocampus. Methods: Evoked and spontaneous inhibitory postsynaptic currents (eIPSCs and sIPSCs) were isolated from CA! pyramidal cells from brain slices of male rats using whole-cell patch-clamp techniques. Results: TL-3 19 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 μM. Conclusion: These data indicate that blockade of μ-opioid receptors by low concentrations of [N-allyl-Dmt[sup1]]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.
- Subjects
ENDORPHIN antagonists; ALCOHOL; NEURAL transmission; GABA receptors; HIPPOCAMPUS (Brain); OPIOIDS; NALTREXONE; NALOXONE; PHARMACOLOGY
- Publication
Alcohol & Alcoholism, 2009, Vol 44, Issue 1, p13
- ISSN
0735-0414
- Publication type
Article
- DOI
10.1093/alcalc/agn085