RT Journal Article
SR Electronic
T1 Actions of ethanol on voltage-sensitive sodium channels: effects of acute and chronic ethanol treatment.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 541
OP 547
VO 242
IS 2
A1 M J Mullin
A1 T K Dalton
A1 W A Hunt
A1 R A Harris
A1 E Majchrowicz
YR 1987
UL http://jpet.aspetjournals.org/content/242/2/541.abstract
AB The effects of acute and chronic ethanol treatment on neurotoxin-stimulated 22Na+ uptake and [3H]batrachotoxinin A20-alpha-benzoate binding to neuronal sodium channels were studied in rat forebrain synaptosomes. Fluorescence measurements were used to assess the intrinsic order or fluidity and the sensitivity to ethanol of rat forebrain synaptic plasma membranes at various intervals during and after chronic ethanol treatment. Acute ethanol administration had no significant effect on neurotoxin binding in the absence or presence of ethanol in vitro or on sodium uptake in the absence of ethanol in vitro. However, a single dose of ethanol produced a dose and time-dependent attenuation of the inhibitory effect of ethanol on sodium uptake, suggestive of acute tolerance. Chronic ethanol treatment reduced the influx of 22Na+ in the presence of batrachotoxin and diminished the inhibitory effect of ethanol in vitro on sodium uptake for up to 20 days after withdrawal, but the specific binding of the neurotoxin in the presence or absence of ethanol was unchanged. Synaptic plasma membranes from chronic ethanol-treated rats showed no change in intrinsic order but the disordering effect of ethanol was significantly smaller for up to 20 days after withdrawal. Results of this study demonstrate that brain tissue from ethanol-treated rats can adapt rapidly to some effects of ethanol and that chronic ethanol administration can reduce the effects of ethanol on physical and functional properties of neurons for a prolonged period of time.