Ethanol suppresses the induction of long-term potentiation in vivo

Givens, Bennet; McMahon, Kathleèn

doi:10.1016/0006-8993(95)00499-g

Cited by 70 publications

(46 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Accordingly, alterations in the kinetics of activation occurred in a critical time frame during which the extent and extant of synaptic transmission is modulated by the strength and duration of the depolarizing impulse. Moreover, the substantial hyperpolarizing shift in the voltage dependence of activation is anticipated to promote synaptic depression through enhanced repolarization, which is consistent with the well known depressant effects of alcohol on target neurons (1,36,37). Indeed, prior reports describe a hyperpolarization of hippocampal neurons by ethanol and propose that an increase in potassium conductance, as demonstrated herein, represents the underlying mechanism (38,39).…”

Section: Discussionsupporting

confidence: 85%

Fatty Acid Ethyl Esters, Nonoxidative Metabolites of Ethanol, Accelerate the Kinetics of Activation of the Human Brain Delayed Rectifier K+ Channel, Kv1.1

Gubitosi-Klug

Gross

1996

Journal of Biological Chemistry

View full text Add to dashboard Cite

Herein we demonstrate that the major metabolites of ethanol in neural tissues, fatty acid ethyl esters, dramatically accelerate the kinetics of the voltage-induced activation of the human brain delayed rectifier potassium channel, Kv1.1. Specifically, the external application of ethyl oleate (20 M) to Sf9 cells expressing the recombinant Kv1.1 channel resulted in a decrease in the rise times of the macroscopic current (e.g. from 51.7 ؎ 13.1 to 12.8 ؎ 3.0 ms at 0 mV for 10 -90% rise times) and a 10-mV hyperpolarizing shift (at 0 mV) in the voltage dependence of channel activation. These effects were dose-dependent (half-maximal effect at 7 M), saturable and specific (i.e. fatty acid methyl esters were without effect). Although application of either ethanol or oleic acid alone did not result in alterations of the activation kinetics, the concomitant application of ethanol and oleic acid reproduced the effects of fatty acid ethyl esters with a temporal course which paralleled the intracellular accumulation of fatty acid ethyl esters in Sf9 cells. Moreover, application of fatty acid ethyl esters (but not ethanol) to rat hippocampal cells in culture produced similar effects on hippocampal delayed rectifier currents. Collectively, these results demonstrate that pathophysiologically relevant concentrations of metabolites of ethanol, fatty acid ethyl esters, modulate the function of a prototypic neuronal ion channel and thus likely contribute to the pathophysiologic sequelae of ethanol abuse in excitable tissues.Elucidation of the biochemical mechanisms underlying the effects of ethanol in electrically excitable tissues has been a long standing goal in neurochemistry (e.g. Refs. 1-3). Due to the structural simplicity of ethanol, the difficulties in identifying the precise biochemical mechanisms responsible for ethanol-induced alterations in electrophysiologic function have represented a fundamental paradox in neuropharmacology. Although multiple effects of ethanol on ion channel function have been demonstrated, consistent alterations in ion channel properties at pathophysiologically relevant concentrations of ethanol (i.e. 0.01-0.1% (2-20 mM)) have not been forthcoming (4 -7). The discordance between the amounts of ethanol necessary to modulate ion channel function in isolated cells and that necessary for perturbation of electrophysiologic function in intact neural structures represents an unresolved and highly controversial issue in the pathobiology of alcohol.Fatty acid ethyl esters are the major nonoxidative metabolite of ethanol in humans and represent the predominant ethanol metabolite in human brain after alcohol ingestion (8 -10). Moreover, detailed examination of fatty acid ethyl ester synthesis in distinct anatomic loci in brain has demonstrated a high correlation between ethanol-induced pathology and the metabolic rates of fatty acid ethyl ester production (11). Since recent studies have identified the electrophysiologic effects of nonesterified fatty acids on ion channels (12-17), we hypothesized that some of...

show abstract

Section: Discussionsupporting

confidence: 85%

Fatty Acid Ethyl Esters, Nonoxidative Metabolites of Ethanol, Accelerate the Kinetics of Activation of the Human Brain Delayed Rectifier K+ Channel, Kv1.1

Gubitosi-Klug

Gross

1996

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Impaired encoding of verbal materials under alcohol has been observed before with slightly higher alcohol doses (Goodwin et al 1969;Petersen 1977). Research in rodents has shown that alcohol distorts the function of the hippocampus and the septohippocampal pathway (Givens 2000;White 2000) and blocks hippocampal long-term potentiation (Sinclair and Lo 1986;Givens and McMahon 1995). An alteration of hippocampal function may in part be the cause of the reduced encoding and, to a smaller extent, retrieval, given the hippocampus' differential involvement in these two processes (Lepage et al 1998).…”

Section: Discussionmentioning

confidence: 91%

Memory encoding and retrieval on the ascending and descending limbs of the blood alcohol concentration curve

et al. 2005

View full text Add to dashboard Cite

show abstract

“…The amnesic effects of alcohol are proposed to be mediated by an effect on the hippocampus and hippocampal circuitry (Anisman, 1972;Gibson, 1985;Ryabinin, 1998;Givens et al, 2000;. This is supported by work demonstrating alcohol-induced impairments in normal hippocampal function (Blitzer et al, 1990;Givens, 1995;Givens and McMahon, 1995) and impairments of memory by acute alcohol in hippocampal-dependent tasks in rats (Givens and McMahon, 1997;Shimizu et al, 1998).…”

Section: Introductionmentioning

confidence: 85%

Alcohol‐induced memory impairment in trace fear conditioning: A hippocampus‐specific effect

Weitemier

Ryabinin

2003

Hippocampus

View full text Add to dashboard Cite

It has been hypothesized that the amnesic effects of alcohol are through selective disruption of hippocampal function. Delay and trace fear conditioning are useful paradigms to investigate hippocampal-dependent and independent forms of memory. With delay fear conditioning, learning of explicit cues does not depend on normal hippocampal function, whereas learning explicit cues in trace fear conditioning does. In both delay and trace fear conditioning, the hippocampus is involved in learning to contextual cues, but it may not be entirely necessary. The present study investigates the effects of alcohol on the acquisition of delay and trace fear conditioning in mice, using freezing as a measure of learning. Male C57BL/6J mice were injected with 0.8 or 1.6 g/kg of 20% v/v alcohol and were immediately exposed to eight tone-footshock pairings in which the conditional stimulus (CS) either coterminated with a footshock unconditional stimulus (US) (delay conditioning) or was separated from the footshock by a 30-s trace interval (trace conditioning). During trace, but not delay fear conditioning, 0.8 g/kg alcohol impaired learning to a tone CS. This dose also impaired context-dependent learning in both procedures (although only slightly for trace fear conditioning). The 1.6 g/kg alcohol exerted a nonselective impairment on learning. The impairment by alcohol of learning to a tone CS when it is hippocampus-dependent, but not when it is hippocampus-independent provides further support for the hypothesis that alcohol exerts a selective effect on hippocampus-dependent learning.

show abstract

Ethanol suppresses the induction of long-term potentiation in vivo

Cited by 70 publications

References 22 publications

Fatty Acid Ethyl Esters, Nonoxidative Metabolites of Ethanol, Accelerate the Kinetics of Activation of the Human Brain Delayed Rectifier K+ Channel, Kv1.1

Fatty Acid Ethyl Esters, Nonoxidative Metabolites of Ethanol, Accelerate the Kinetics of Activation of the Human Brain Delayed Rectifier K+ Channel, Kv1.1

Memory encoding and retrieval on the ascending and descending limbs of the blood alcohol concentration curve

Alcohol‐induced memory impairment in trace fear conditioning: A hippocampus‐specific effect

Contact Info

Product

Resources

About