GABAergic miniature postsynaptic currents in septal neurons show differential allosteric sensitivity after binge-like ethanol exposure

Brain Research
Dustin W DuBoisG D Frye

Abstract

Binge-like ethanol treatment of septal neurons blunts GABAAR-mediated miniature postsynaptic currents (mPSCs), suggesting it arrests synaptic development. Ethanol may disrupt postsynaptic maturation by blunting feedback signaling through immature GABAARs. Here, the impact of ethanol on the sensitivity of mPSCs to zolpidem, zinc and 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha-OH-DHP) was tested. The decay phase of mPSCs showed concentration-dependent potentiation by zolpidem (0.03-100 microM), which was substantially blunted after ethanol exposure. Since zolpidem potentiation exhibited a substantial age-dependent increase in untreated neurons, this finding supported the idea that ethanol arrests synaptic development. GABAAR alpha1 subunit protein also increased with age in untreated neurons, paralleling enhanced sensitivity to zolpidem. Surprisingly, alpha1 levels were not reduced by binge ethanol even though mPSCs were relatively zolpidem-insensitive. Zinc (3-30 microM) decreased mPSC parameters in a concentration- and age-related manner with older untreated cells showing less inhibition. However, there was no increase in mPSC zinc sensitivity after binge ethanol as would be expected if a general arrest of synaptic maturation ...Continue Reading

References

Feb 1, 1992·Brain Research. Molecular Brain Research·T Araki, M Tohyama
Jul 9, 1990·Brain Research·J D BrioniJ L McGaugh
Sep 1, 1995·Brain Research. Molecular Brain Research·N G Weiland, M Orchinik
Oct 23, 1997·Neuroreport·L V ColomS H Appel
Dec 11, 1997·Neurotoxicology and Teratology·C R Goodlett, T B Johnson
Jan 12, 2000·Alcoholism, Clinical and Experimental Research·A L MorrowK A Grant
Jun 1, 2000·Alcoholism, Clinical and Experimental Research·E T CostaC F Valenzuela
Dec 18, 2001·Brain Research. Brain Research Reviews·A L MorrowD B Matthews
Feb 13, 2002·Alcohol·J A Mennella, P L Garcia-Gomez
Jul 11, 2002·Annals of Medicine·John W OlneyChrysanthy Ikonomidou
Feb 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·Marisa RobertoGeorge R Siggins
Apr 16, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mario CartaC Fernando Valenzuela
Jul 23, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Enrico SannaGiovanni Biggio
Sep 3, 2004·Journal of Neurochemistry·Jerri C CaldeiraC Fernando Valenzuela
Sep 8, 2004·Brain Research. Developmental Brain Research·Dustin W DuBoisGerald D Frye
Sep 24, 2004·The European Journal of Neuroscience·Andrea BarberisEnrico Cherubini
Nov 27, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Olusegun J Ariwodola, Jeffrey L Weiner
Jun 2, 2005·Trends in Neurosciences·Alfonso Represa, Yehezkel Ben-Ari

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