Ethanol inhibition of glycine-activated responses in neurons of ventral tegmental area of neonatal rats

Jiang Ye, Liang Tao, L. I. Zhu, Krešimir Krnjević, Joseph J. Mcardle

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Abstract

The brain is particularly sensitive to alcohol during the period of its rapid growth. To better understand the mechanism(s) involved, we studied ethanol effects on glycine-activated responses of ventral tegmental area (VTA) neurons isolated from the newborn rat, using whole cell and gramicidin perforated patch-clamp techniques. Previously we reported that 0.1-40 mM ethanol enhances glycine-induced responses of 35% of VTA neurons (Ye et al. 2001). We now direct our attention to the inhibitory effects of ethanol observed in 45% (312 of 694) of neonatal VTA neurons. Under current-clamp conditions, 1 mM ethanol had no effect on the membrane potential of these cells, but it decreased glycine-induced membrane depolarization and the frequency of spontaneous action potentials. Under voltage-clamp conditions, 0.1-10 mM ethanol did not elicit a current but depressed the glycine-induced currents. The ethanol-induced inhibition of glycine current was independent of membrane potential (between -60 and +60 mV). Likewise, ethanol did not alter the reversal potential of the glycine-activated currents. Ethanol-mediated inhibition of glycine current depended on the glycine concentration. While ethanol strongly depressed currents activated by 30 μM glycine, it had no appreciable effect on maximal currents activated by 1 mM glycine. In the presence of ethanol (1 mM), the EC50 for glycine increased from 32 ± 5 to 60 ± 3 μM. Thus ethanol may decrease the agonist affinity of glycine receptors. A kinetic analysis indicated that ethanol shortens the time constant of glycine current deactivation but has no effect on activation. In conclusion, by altering VTA neuronal function, ethanol-induced changes in glycine receptors may contribute to neurobehavioral manifestations of the fetal alcohol syndrome.

Original languageEnglish (US)
Pages (from-to)2426-2434
Number of pages9
JournalJournal of Neurophysiology
Volume86
Issue number5
StatePublished - Dec 1 2001

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

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