Ethanol inhibition of glycine-activated responses in neurons of ventral tegmental area of neonatal rats.
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.
Ye
J H
JH
Department of Anesthesiology, New Jersey Medical School, Newark, New Jersey 07103-2714, USA. ye@umdnj.edu
Tao
L
L
Zhu
L
L
Krnjević
K
K
McArdle
J J
JJ
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
D018009:Receptors, Glycine; D011978:Receptors, Nicotinic; D000431:Ethanol; D015032:Zinc; D005998:Glycine