Ethanol blocks long-term potentiation of GABAergic synapses in the ventral tegmental area involving mu-opioid receptors.
Ethanol blocks long-term potentiation of GABAergic synapses in the ventral tegmental area involving mu-opioid receptors.
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DOI：
10.1038/npp.2010.51
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发表时间：
2010-08
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It is well documented that ethanol exposure alters GABA (γ-aminobutyric acid)-releasing synapses, and ethanol addiction is associated with endogenous opioid system. Emerging evidence indicates that opioids block long-term potentiation in the fast inhibitory GABAA receptor synapses (LTPGABA) onto dopamine-containing neurons in the ventral tegmental area (VTA), a brain region essential for reward-seeking behavior. However, how ethanol affects LTPGABA is not known. We report here that in acute midbrain slices from rats, clinically relevant concentrations of ethanol applied both in vitro and in vivo prevents LTPGABA, which is reversed respectively by in vitro and in vivo administration of naloxone, a μ opioid receptor (MOR) antagonist. Furthermore, the blockade of LTPGABA induced by a brief in vitro ethanol treatment is mimicked by DAMGO ([D-Ala2, N-MePhe4, Gly-ol]-enkephalin), a MOR agonist. Pared-pulse ratios are similar in slices 24 hours after in vivo injection with either saline or ethanol. Sp-cAMPS, a stable cAMP analog, and pCPT-cGMP, a cGMP analogue potentiates GABAA-mediated IPSCs in slices from ethanol treated rats, indicating that a single in vivo ethanol exposure does not maximally increase GABA release; instead, ethanol produces a long-lasting inability to generate LTPGABA. These neuroadaptations to ethanol might contribute to early stage of addiction.
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DOI：
10.1038/npp.2008.143
发表时间：
2009-04
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
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作者：
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影响因子：
5.5
作者：
JOHNSON, SW;NORTH, RA
通讯作者：
NORTH, RA
影响因子：
5.5
作者：
Nugent, Fereshteh S.;Kauer, Julie A.
通讯作者：
Kauer, Julie A.
影响因子：
4.7
作者：
Bergevin, A;Girardot, D;Trudeau, LE
通讯作者：
Trudeau, LE
影响因子：
3.6
作者：
Krishnan-Sarin, S;Wand, GS;Froehlich, JC
通讯作者：
Froehlich, JC