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 rap id growth. To better understand the mechanism(s) involved, we studied ethan ol effects on glycine-activated responses of ventral tegmental area (VTA) n eurons isolated from the newborn rat, using whole cell and gramicidin perfo rated 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 s pontaneous action potentials. Under voltage-clamp conditions, 0.1-10 mM eth anol did not elicit a current but depressed the glycine-induced currents. T he ethanol-induced inhibition of glycine current was independent of membran e potential (between -60 and +60 mV). Likewise, ethanol did not alter the r eversal potential of the glycine-activated currents. Ethanol-mediated inhib ition of glycine current depended on the glycine concentration. While ethan ol strongly depressed currents activated by 30 muM glycine, it had no appre ciable effect on maximal currents activated by 1 mM glycine. In the presenc e of ethanol (1 mM), the EC50 for glycine increased from 32 +/- 5 to 60 +/- 3 muM. Thus ethanol may decrease the agonist affinity of glycine receptors . A kinetic analysis indicated that ethanol shortens the time constant of g lycine current deactivation but has no effect on activation. In conclusion, by altering VTA neuronal function, ethanol-induced changes in glycine rece ptors may contribute to neurobehavioral manifestations of the fetal alcohol syndrome.