The Journal of Neurophysiology Vol. 86 No. 5 November 2001, pp. 2426-2434
Copyright ©2001 by the American Physiological Society

Ethanol Inhibition of Glycine-Activated Responses in Neurons of Ventral Tegmental Area of Neonatal Rats

Jiang Hong Ye,¹ Liang Tao,¹ Li Zhu,¹ Kreimir Krnjevi,² and Joseph J. McArdle¹

 ¹Departments of Anesthesiology and Pharmacology and Physiology, New Jersey Medical School, Newark, New Jersey 07103-2714; and  ²Anaesthesia Research Department, McGill University, Montreal, Quebec H3G 1Y6, Canada

Ye, Jiang Hong, Liang Tao, Li Zhu, Kreimir Krnjevi, and Joseph J. McArdle. Ethanol Inhibition of Glycine-Activated Responses in Neurons of Ventral Tegmental Area of Neonatal Rats. J. Neurophysiol. 86: 2426-2434, 2001. 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.