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Inhibition by ethanol of NMDA-induced responses and acute tolerance to the inhibition in rat sympathetic preganglionic neurons in vitro and in vivo.

Abstract：

:N-methyl-d-aspartate (NMDA) receptors have been demonstrated to be a pivotal target for ethanol action. The present study examined the actions of acute ethanol exposure on NMDA-induced responses and the acute tolerance to ethanol actions in rat sympathetic preganglionic neurons (SPNs) in vitro and in vivo. NMDA (50 microM) applied every 5 min induced reproducible membrane depolarizations of SPNs in neonatal spinal cord slice preparations. Ethanol (50 - 100 mM) applied by superfusion for 15 min caused a sustained decrease in NMDA-induced depolarizations in a dose-dependent and reversible manner. When the superfusion time of ethanol (100 mm) was increased to 50 min, NMDA-induced depolarizations were attenuated initially but a gradual recovery was seen in approximately 40% of SPNs tested. Repeated injections of NMDA (2 nM) intrathecally at 30 min interval caused reproducible increases in mean arterial pressure (MAP) in urethane-anesthetized rats. Intravenous injections of ethanol (0.16 or 0.32 g, 1 ml) inhibited NMDA-induced pressor effects in a blood concentration-dependent manner. The inhibition by ethanol of NMDA-induced pressor effects was reduced over time during continuous infusion of ethanol or on the second injection 3.5 h after prior injection of a higher dose of ethanol. Ethanol, at concentrations significantly inhibited NMDA-induced responses, had no significant effects on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced responses. The study demonstrated the selective inhibition by ethanol of NMDA-induced responses and the development of acute tolerance to the inhibitory effects in SPNs both in vitro and in vivo. These effects may play important roles in the ethanol regulation of cardiovascular function.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Lin HH,Hsieh WK,Shiu JY,Chiu TH,Lai CC

doi

10.1038/sj.bjp.0705512

subject

Has Abstract

pub_date

2003-11-01 00:00:00

pages

955-63

issue

eissn

0007-1188

issn

1476-5381

pii

sj.bjp.0705512

journal_volume

140

pub_type

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Inhibition by ethanol of NMDA-induced responses and acute tolerance to the inhibition in rat sympathetic preganglionic neurons in vitro and in vivo.