title: Ethanol blocks long-term potentiation of GABAergic synapses in the ventral tegmental area involving mu-opioid receptors.
abstract: It is well documented that ethanol exposure alters GABA (gamma-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 GABA(A) receptor synapses (LTP(GABA)) onto dopamine-containing neurons in the ventral tegmental area (VTA), a brain region essential for reward-seeking behavior. However, how ethanol affects LTP(GABA) 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 LTP(GABA), which is reversed, respectively, by in vitro and in vivo administration of naloxone, a mu-opioid receptor (MOR) antagonist. Furthermore, the blockade of LTP(GABA) induced by a brief in vitro ethanol treatment is mimicked by DAMGO ([D-Ala(2), N-MePhe(4), 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 GABA(A)-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 LTP(GABA). These neuroadaptations to ethanol might contribute to early stage of addiction.
authors.affiliation: Department of Anesthesiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Yan-zhong
authors.initials: YZ
authors.lastname: Guan
authors.forename: Jiang-Hong
authors.initials: JH
authors.lastname: Ye
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D017774:Long-Term Potentiation / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000166:cytology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; C474799:CPT-cGMP; D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D017450:Receptors, Opioid, mu; D013873:Thionucleotides; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C016957:adenosine-3',5'-cyclic phosphorothioate; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D000242:Cyclic AMP; D006152:Cyclic GMP; D004298:Dopamine
references.citation: J Neurosci. 1997 Jan 15;17(2):796-803
references.pmid: 8987801
references.citation: Neuroscience. 2008 Apr 22;153(1):240-8
references.pmid: 18343590
references.citation: Annu Rev Neurosci. 2006;29:565-98
references.pmid: 16776597
references.citation: Neuropsychopharmacology. 2009 Jun;34(7):1829-42
references.pmid: 19194373
references.citation: Alcohol. 2000 Oct;22(2):85-90
references.pmid: 11113622
references.citation: Physiol Behav. 2004 Apr;81(2):339-58
references.pmid: 15159175
references.citation: Neuropsychopharmacology. 2009 Apr;34(5):1233-44
references.pmid: 18784647
references.citation: Synapse. 2001 Sep 15;41(4):311-28
references.pmid: 11494402
references.citation: Alcohol Clin Exp Res. 2008 Jun;32(6):1040-8
references.pmid: 18422836
references.citation: Eur J Neurosci. 2009 Jul;30(2):272-8
references.pmid: 19614973
references.citation: Neuroscience. 2004;127(3):777-84
references.pmid: 15283974
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2938-42
references.pmid: 16477003
references.citation: Neuropsychopharmacology. 2009 Jan;34(2):307-18
references.pmid: 18596684
references.citation: Alcohol. 2003 Apr;29(3):165-71
references.pmid: 12798972
references.citation: J Neurosci. 2004 Oct 13;24(41):8961-74
references.pmid: 15483115
references.citation: J Neurosci. 1998 Oct 1;18(19):8003-15
references.pmid: 9742167
references.citation: Pharmacol Ther. 2005 Jul;107(1):80-98
references.pmid: 15963352
references.citation: Pharmacol Ther. 2006 Sep;111(3):533-54
references.pmid: 16427127
references.citation: Proc Natl Acad Sci U S A. 1986 Jun;83(11):4071-5
references.pmid: 2424017
references.citation: J Neurosci. 2002 Mar 15;22(6):2074-82
references.pmid: 11896147
references.citation: Psychopharmacology (Berl). 2008 Dec;201(2):261-71
references.pmid: 18688603
references.citation: J Neurosci. 2008 Nov 26;28(48):12672-81
references.pmid: 19036960
references.citation: Pharmacol Biochem Behav. 1998 Mar;59(3):627-35
references.pmid: 9512064
references.citation: Neuron. 2008 Jul 31;59(2):288-97
references.pmid: 18667156
references.citation: J Physiol. 2007 May 1;580(Pt.3):731-43
references.pmid: 17303643
references.citation: J Neurosci. 2001 Dec 1;21(23):RC184
references.pmid: 11717387
references.citation: Nature. 2007 Apr 26;446(7139):1086-90
references.pmid: 17460674
references.citation: Curr Drug Abuse Rev. 2008 Jun;1(2):239-52
references.pmid: 19630722
references.citation: J Neurosci Methods. 2006 Dec 15;158(2):251-9
references.pmid: 16842860
references.citation: Trends Pharmacol Sci. 1992 May;13(5):185-93
references.pmid: 1604711
references.citation: Annu Rev Physiol. 2002;64:355-405
references.pmid: 11826273
references.citation: J Pharmacol Exp Ther. 1999 Dec;291(3):1045-53
references.pmid: 10565823
references.citation: Nat Rev Neurosci. 2001 Oct;2(10):695-703
references.pmid: 11584307
references.citation: Psychopharmacology (Berl). 1997 Jan;129(2):99-111
references.pmid: 9040115
references.citation: Alcohol Clin Exp Res. 2007 Jul;31(7):1106-13
references.pmid: 17577392
references.citation: J Neurosci. 2003 Nov 5;23(31):9981-6
references.pmid: 14602811
references.citation: Alcohol Clin Exp Res. 2001 Jan;25(1):25-33
references.pmid: 11198711
references.citation: Trends Neurosci. 1995 Jan;18(1):22-9
references.pmid: 7535487
references.citation: Synapse. 2001 Sep 1;41(3):221-9
references.pmid: 11418935
references.citation: Synapse. 1993 Jan;13(1):63-73
references.pmid: 8427014
references.citation: Alcohol Clin Exp Res. 2009 Jun;33(6):1033-43
references.pmid: 19302084
references.citation: J Physiol. 2008 Mar 15;586(6):1487-93
references.pmid: 18079157
references.citation: J Pharmacol Exp Ther. 2009 May;329(2):625-33
references.pmid: 19225162
references.citation: J Physiol. 1992 May;450:455-68
references.pmid: 1331427
references.citation: Neurochem Int. 1999 Aug;35(2):115-23
references.pmid: 10405995
references.citation: Nat Rev Neurosci. 2007 Nov;8(11):844-58
references.pmid: 17948030
references.citation: Neurosci Res. 2003 Oct;47(2):153-60
references.pmid: 14512140
references.citation: J Neurosci. 1992 Feb;12(2):483-8
references.pmid: 1346804
references.citation: Neuropharmacology. 2002 Jun;42(8):1065-78
references.pmid: 12128008
references.citation: J Pharmacol Exp Ther. 2004 Oct;311(1):282-9
references.pmid: 15169831