title: Ethanol inhibition of glycine-activated responses in neurons of ventral tegmental area of neonatal rats.
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. 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 microM glycine, it had no appreciable effect on maximal currents activated by 1 mM glycine. In the presence of ethanol (1 mM), the EC(50) for glycine increased from 32 +/- 5 to 60 +/- 3 microM. 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.
authors.affiliation: Department of Anesthesiology, New Jersey Medical School, Newark, New Jersey 07103-2714, USA. ye@umdnj.edu
authors.forename: J H
authors.initials: JH
authors.lastname: Ye
authors.forename: L
authors.initials: L
authors.lastname: Tao
authors.forename: L
authors.initials: L
authors.lastname: Zhu
authors.forename: K
authors.initials: K
authors.lastname: Krnjević
authors.forename: J J
authors.initials: JJ
authors.lastname: McArdle
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D004340:Drug Contamination; D004553:Electric Conductivity; D000431:Ethanol / Q000494:pharmacology*; D005998:Glycine / Q000494:pharmacology*; D007700:Kinetics; D009433:Neural Inhibition; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D015032:Zinc / Q000494:pharmacology
chemical_list: D018009:Receptors, Glycine; D011978:Receptors, Nicotinic; D000431:Ethanol; D015032:Zinc; D005998:Glycine