Abstract
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. Paired-pulse ratios are similar in slices, 24 h after in vivo injection with either saline or ethanol. Sp-cAMPS, a stable cAMP analog, and pCPT-cGMP, a cGMP analog, potentiates GABAA-mediated inhibitory postsynaptic currents 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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Acknowledgements
This work was made possible by the support of NIH grants to JHY (R01AA016964; R21AA015925 and R21AA016618). We are grateful to Dr K Krnjevic’ for his helpful comments on this work.
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Guan, Yz., Ye, JH. Ethanol Blocks Long-Term Potentiation of GABAergic Synapses in the Ventral Tegmental Area Involving μ-Opioid Receptors. Neuropsychopharmacol 35, 1841–1849 (2010). https://doi.org/10.1038/npp.2010.51
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DOI: https://doi.org/10.1038/npp.2010.51
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