The Gamma‐aminobutyric Acid (Gaba) System in Brain During Acute and Chronic Ethanol Intoxication

Sytinsky, I.A.; Guzikov, B. M.; Gomanko, M. V.; Eremin, V. P.; Konovalova, N. N.

doi:10.1111/j.1471-4159.1975.tb07691.x

Cited by 136 publications

(31 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is also interesting that ethanol, like pentobarbital, produces a biphasic effect on 36Cl-uptake. Ethanol has previously been reported to have a biphasic effect on both the brain concentration and turnover of GABA (42,43). However, it is more likely that the decrease in ethanol-stimulated 36Cl-uptake observed at higher ethanol concentrations is due to an ethanol-induced state of receptor desensitization.…”

Section: Discussionmentioning

confidence: 99%

Ethanol stimulates gamma-aminobutyric acid receptor-mediated chloride transport in rat brain synaptoneurosomes.

Suzdak¹,

Schwartz²,

Skolnick³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

429

179

View full text Add to dashboard Cite

The effects of ethanol on Cl-uptake were studied using a cell-free subcellular preparation from brain that contains a y-aminobutyric acid (GABA)/barbiturate receptor-sensitive Cl transport system. In isolated vesicles prepared from rat cerebral cortex, ethanol, at concentrations that are present during acute intoxication (20-50 mM), stimulated 36CI-uptake in a concentration-dependent and biphasic manner. The ethanol-stimulated uptake of 36CI-was markedly inhibited by the GABA antagonists picrotoxin and bicuculline but not by a variety of other neurotransmitter receptor antagonists. The effects of ethanol in stimulating 36CI-uptake in isolated brain vesicles were qualitatively and quantitatively similar to that of pentobarbital. Ethanol also markedly potentiated both muscimol-and pentobarbital-stimulated 36CI-uptake at concentrations below those that directly stimulate Cl-uptake. Under our incubation conditions, ethanol did not release GABA, suggesting that it interacts with the postsynaptic GABA/barbiturate receptor complex. The ability of ethanol to stimulate GABA/barbiturate receptor-mediated Cl-transport may explain many of its pharmacological properties and provides a mechanism for the common psychopharmacological actions of ethanol, barbiturates, and benzodiazepines.Ethanol is one of the oldest and most commonly used of all psychotropic drugs (1). Repeated exposure to ethanol produces both psychological and physical dependence and its abuse potential constitutes a major public health problem (2). The neurochemical mechanism(s) underlying the depressant effects of ethanol on the central nervous system (CNS) is poorly understood (3) despite numerous studies demonstrating effects of ethanol on several neurotransmitter systems (4, 5). Ethanol shares many pharmacologic actions with both barbiturates and benzodiazepines. For example, ethanol, like barbiturates and benzodiazepines, possesses anxiolytic and sedative/hypnotic activity in both laboratory animals (6, 7) and humans (8). Moreover, previous studies have documented the development of behavioral cross-tolerance between ethanol, barbiturates, and benzodiazepines (9, 10). Benzodiazepines and barbiturates, which also show crossdependence with each other, are effective in alleviating the withdrawal symptoms that occur after chronic ethanol administration, suggesting that all three drugs may share a common mechanism of action (11).It is now generally accepted that both benzodiazepines and barbiturates produce their major pharmacological effects by augmenting the actions of the principal inhibitory neurotransmitter of brain, y-aminobutyric acid (GABA) (12)(13)(14)(15) ly associated with the Cl-channel in both rat and mouse brain membranes (25,26). Unfortunately, the concentrations of ethanol used in many of these receptor binding studies exceed those observed during acute intoxication (>30 mM) and are, in fact, many times above the lethal concentration (>100 mM) (27,28).Recently, we have reported the use of the "synaptoneurosome," a subcellular brain pre...

show abstract

Section: Discussionmentioning

confidence: 99%

Ethanol stimulates gamma-aminobutyric acid receptor-mediated chloride transport in rat brain synaptoneurosomes.

Suzdak¹,

Schwartz²,

Skolnick³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

429

179

View full text Add to dashboard Cite

show abstract

“…The inconsistency may be due to a biphasic dose-dependent response of GABA to ethanol. Results indicate that glutamine and GABA increase at low-level exposure (2 g/kg ethanol) but decrease at higher exposure concentrations (3 and 8 g/kg) (94). Not all studies on the neurochemical effects of alcohol have focused on the GABAergic system.…”

Section: Ethanolmentioning

confidence: 92%

“…In addition, studies using animal models have investigated the neuroanatomical and neurochemical effects of prenatal alcohol exposure. Most of the studies concerning the neurochemical effects have focused on the GABAergic system (93,94). The results of these studies, however, have not provided a consistent pattern of effects.…”

Section: Ethanolmentioning

confidence: 97%

Neurotoxic effects of gasoline and gasoline constituents.

Burbacher

1993

Environ Health Perspect

View full text Add to dashboard Cite

This overview was developed as part of a symposium on noncancer end points of gasoline and key gasoline components. The specific components included are methyl tertiary butyl ether, ethyl tertiary butyl ether, tertiary amyl methyl ether, butadiene, benzene, xylene, toluene, methyl alcohol, and ethyl alcohol. The overview focuses on neurotoxic effects related to chronic low-level exposures. A few general conclusions and recommendations can be made based on the results of the studies to date. a) All the compounds reviewed are neuroactive and, as such, should be examined for their neurotoxicity. b) For most of the compounds, there is a substantial margin of safety between the current permissible exposure levels and levels that would be expected to cause overt signs of neurotoxicity in humans. This is not the case for xylene, toluene, and methanol, however, where neurologic effects are observed at or below the current Threshold Limit Value. c) For most of the compounds, the relationship between chronic low-level exposure and subtle neurotoxic effects has not been studied. Studies therefore should focus on examining the dose-response relationship between chronic low-level exposure and subtle changes in central nervous system function.

show abstract

“…An acute injection of ethanol (2 to 8 g/kg) was found to decrease cerebellar and cortical levels of glutamate, 140 although the higher doses had no greater effect than the lowest dose. 140 After chronic exposure of rats to ethanol for 2 weeks or longer, glutamic acid was increased in the cortex, hippocampus, and substantia nigra 140 · 142 and remained low in the cerebellum.…”

Section: Glutamatementioning

confidence: 92%

“…140 After chronic exposure of rats to ethanol for 2 weeks or longer, glutamic acid was increased in the cortex, hippocampus, and substantia nigra 140 · 142 and remained low in the cerebellum. 140 The caveat regarding difficulties in distinguishing between neurotransmitter and metabolic pools of glutamate has to be considered in interpretation of these studies, just as this caveat has to be considered in evaluating the effects of ethanol on GABA levels.…”

Section: Glutamatementioning

confidence: 98%