Effect of ethanol upon respiratory-related hypoglossal nerve output of neonatal rat brain stem slices

The actions of ethanol (EtOH) on the respiratory output of the neonatal rat brain stem slice preparation in vitro are described. Ethanol inhibited res pirator-related hypoglossal nerve activity in a dose-dependent manner. The effect of EtOH was evident within 5 min and was reversible on EtOH washout. The actions of EtOH were qualitatively similar to those of two other alcoh ols, methanol and octanol. We investigated the dose response relationship f or each alcohol and determined that the order of potency was methanol < EtO H much less than octanol, with EC50 values of 291 mM, 39.7 mM, and 49.2 mu M respectively. Application of either strychnine (5 mu M) or bicuculline (5 mu M) alone, partially but not significantly, reversed the inhibition of r espiratory-related hypoglossal nerve activity produced by 50 mM EtOH. Prein cubation of rhythmic slices with a combination of both strychnine and bicuc ulline (both 5 mu M) partially, but significantly, blocked the inhibitory a ctions of EtOH, suggesting that other mechanisms also play a role in the ac tion of EtOH. Preincubation of the slices with 25 mu M APV reduced the rela tive degree of inhibition caused by EtOH suggesting that N-methyl-D-asparta te (NMDA)-receptor-mediated events can be affected by EtOH. Furthermore inh ibition of protein kinase C by incubation with 100 nM staurosporine also re duced the efficacy of EtOH. These results suggest that the actions of EtOH may be mediated via glycine, GABA(A), and NMDA receptors and that activatio n of protein kinase C is involved in the EtOH-induced inhibition of respira tory-related hypoglossal nerve activity.