Effect Of Ethanol Upon Respiratory-Related Hypoglossal Nerve Output Of Neonatal Rat Brainstem Slices. Ian C. Gibson and Albert J. Berger. Department of Physiology and Biophysics, School of Medicine, University of Washington, Box 357290, Seattle, WA 98195-7290.
APStracts 6:0490N, 1999.
The actions of ethanol (EtOH) upon the respiratory output of the neonatal rat brainstem slice preparation in vitro are described. Ethanol inhibited respiratory-related hypoglossal nerve activity in a dose-dependent manner. The effect of EtOH was evident within 5 minutes and was reversible upon EtOH washout. The actions of EtOH were qualitatively similar to those of two other alcohols, methanol and octanol. We investigated the dose-response relationship for each alcohol and determined that the order of potency was methanol < EtOH << octanol, with EC50 values of 291 mM, 39.7 mM and 49.2 (M respectively. Application of either strychnine (5 ?M) or bicuculline (5 ?M) alone, partially but not significantly, reversed the inhibition of respiratory-related hypoglossal nerve activity produced by 50 mM EtOH. Pre-incubation of rhythmic slices with a combination of both strychnine and bicuculline (both 5 ?M) partially, but significantly, blocked the inhibitory actions of EtOH suggesting that other mechanisms also play a role in the action of EtOH. Pre-incubation of the slices with 25 ?M APV reduced the relative degree of inhibition caused by EtOH suggesting that NMDA receptor-mediated events can be affected by EtOH. Furthermore, inhibition of protein kinase C by incubation with 100 nM staurosporine also reduced the efficacy of EtOH. These results suggest that the actions of EtOH may be mediated via glycine, GABAA and NMDA receptors and that activation of protein kinase C is involved in the EtOH-induced inhibition of respiratory-related hypoglossal nerve activity.
Received 7 June 1999; accepted in final form 20 September 1999.
APS Manuscript Number J464-9.
Article publication pending Journal of Neurophysiology.
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 21 December 1999