Characterization of the phenomenon of rapid tolerance to ethanol

Khanna, J. M.; Chau, A.; Shah, G.

doi:10.1016/s0741-8329(96)00083-3

Cited by 38 publications

(29 citation statements)

References 18 publications

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“…Importantly, these changes are fully reversible by 2 weeks or less after intoxication, unlike the persistent alterations induced by CIE treatment. Acute tolerance to EtOH enhancement of GABA A R-mediated I tonic is observed within 1 h after in vivo EtOH exposure, suggesting that this physiological mechanism may underlie the acute behavioral tolerance to EtOH observed in animals and humans, (Khanna et al, 1996;Fillmore et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…We were also intrigued by the possibility that the demonstrated development of rapid EtOH tolerance in rodents (Khanna et al, 1996;Wu et al, 1996;Ludvig et al, 2001) and in humans (Hurst and Bagley, 1972;Fillmore et al, 2005) may be mediated by functional alterations in GABA A Rs. Therefore, we set out to determine whether the function and subunit composition of GABA A Rs may be altered after a single intoxicating dose of EtOH and to examine some of the mechanisms of such alterations in the hippocampal CA1 and dentate gyrus regions.…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms of Reversible GABA_AReceptor Plasticity after Ethanol Intoxication

Liang¹,

Suryanarayanan²,

Abriam³

et al. 2007

J. Neurosci.

142

211

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The time-dependent effects of ethanol (EtOH) intoxication on GABA A receptor (GABA A R) composition and function were studied in rats. A cross-linking assay and Western blot analysis of microdissected CA1 area of hippocampal slices obtained 1 h after EtOH intoxication (5 g/kg, gavage), revealed decreases in the cell-surface fraction of ␣4 and ␦, but not ␣1, ␣5, or ␥2 GABA A R subunits, without changes in their total content. This was accompanied (in CA1 neuron recordings) by decreased magnitude of the picrotoxin-sensitive tonic current (I tonic ), but not miniature IPSCs (mIPSCs), and by reduced enhancement of I tonic by EtOH, but not by diazepam. By 48 h after EtOH dosing, cell-surface ␣4 (80%) and ␥2 (82%) subunit content increased, and cell-surface ␣1 (Ϫ50%) and ␦ (Ϫ79%) and overall content were decreased. This was paralleled by faster decay of mIPSCs, decreased diazepam enhancement of both mIPSCs and I tonic , and paradoxically increased mIPSC responsiveness to EtOH (10 -100 mM). Sensitivity to isoflurane-or diazepam-induced loss of righting reflex was decreased at 12 and 24 h after EtOH intoxication, respectively, suggesting functional GABA A R tolerance. The plastic GABA A R changes were gradually and fully reversible by 2 weeks after single EtOH dosing, but unexplainably persisted long after withdrawal from chronic intermittent ethanol treatment, which leads to signs of alcohol dependence. Our data suggest that early tolerance to EtOH may result from excessive activation and subsequent internalization of ␣4␤␦ extrasynaptic GABA A Rs. This leads to transcriptionally regulated increases in ␣4 and ␥2 and decreases in ␣1 subunits, with preferential insertion of the newly formed ␣4␤␥2 GABA A Rs at synapses.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mechanisms of Reversible GABA_AReceptor Plasticity after Ethanol Intoxication

Liang¹,

Suryanarayanan²,

Abriam³

et al. 2007

J. Neurosci.

142

211

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“…[6][7][35][36][37][38] In addition, studies carried out by Khanna et al revealed that rapid tolerance occurs when ethanol is administered on both test days (intoxicated practice) and also in the dummy test (measurements were not actually recorded until the second day of the protocol), suggesting that the behavioral experience on an inclined plane or on the hypothermia test is not crucial for the development of rapid tolerance to ethanol. 36 Our results are also in accordance with those of that study since our animals were tested in the elevated plus-maze only on the second day. Moreover, the results of studies carried out by Bertoglio & Carobrez suggest that previous experience in the elevated plus-maze affects the anxiolytic effect of ethanol and of phenobarbital, a phenomenon known as "one-trial tolerance".…”

Section: Discussionmentioning

confidence: 99%

Effect of isopregnanolone on rapid tolerance to the anxiolytic effect of ethanol

Debatin

Barbosa

2006

Rev. Bras. Psiquiatr.

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Effect of isopregnanolone on rapid tolerance to the anxiolytic effect of ethanol Influência da isopregnenolona na tolerância rápida ao efeito ansiolítico do etanol A b s t r a c t Objective: It has been shown that neurosteroids can either block or stimulate the development of chronic and rapid tolerance to the incoordination and hypothermia caused by ethanol consumption. The aim of the present study was to investigate the influence of isopregnanolone on the development of rapid tolerance to the anxiolytic effect of ethanol in mice. Method: Male Swiss mice were pretreated with isopregnanolone (0.05, 0.10 or 0.20 mg/kg) 30 min before administration of ethanol (1.5 g/kg). Twenty-four hours later, all animals we tested using the plus-maze apparatus. The first experiment defined the doses of ethanol that did or did not induce rapid tolerance to the anxiolytic effect of ethanol. In the second, the influence of pretreatment of mice with isopregnanolone (0.05, 0.10 or 0.20 mg/kg) on rapid tolerance to ethanol (1.5 g/kg) was studied. Conclusions: The results show that pretreatment with isopregnanolone interfered with the development of rapid tolerance to the anxiolytic effect of ethanol.Keywords: Ethanol; Drug tolerance; Anti-anxiety agents; Mice; Alcoholism

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“…Because octopamine in invertebrates is thought to be functionally homologous to noradrenaline in vertebrates (reviewed in Evans, 1980;Roeder, 1999), these data demonstrate interesting similarities among the mechanisms of ethanol tolerance in flies and mammals. In addition, several quantitative aspects of tolerance, such as the extent of maximal tolerance and its duration (about 24 h), are also comparable in flies and rodents (Khanna et al, 1991(Khanna et al, , 1996. This opens the door for a genetic analysis of tolerance in Drosophila, an approach that will likely provide much needed molecular insight into the process in mammals, including humans.…”

Section: Ethanol Tolerance In Drosophilamentioning

confidence: 94%

Invertebrate models of drug abuse

2002

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Susceptibility to drug addiction depends on genetic and environmental factors and their complex interactions. Studies with mammalian models have identified molecular targets, neurochemical systems, and brain regions that mediate some of the addictive properties of abused drugs. Yet, our understanding of how the primary effects of drugs lead to addiction remains incomplete. Recently, researchers have turned to the invertebrate model systems Drosophila melanogaster and Caenorhabditis elegans to dissect the mechanisms by which abused drugs modulate behavior. Due to their sophisticated genetics, relatively simple anatomy, and their remarkable molecular similarity to mammals, these invertebrate models should provide useful insights into the mechanisms of drug action. Here we review recent behavioral and genetic studies in flies and worms on the effects of ethanol, cocaine, and nicotine, three of the most widely abused drugs in the world.

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Characterization of the phenomenon of rapid tolerance to ethanol

Cited by 38 publications

References 18 publications

Mechanisms of Reversible GABA_AReceptor Plasticity after Ethanol Intoxication

Mechanisms of Reversible GABA_AReceptor Plasticity after Ethanol Intoxication

Effect of isopregnanolone on rapid tolerance to the anxiolytic effect of ethanol

Invertebrate models of drug abuse

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Characterization of the phenomenon of rapid tolerance to ethanol

Cited by 38 publications

References 18 publications

Mechanisms of Reversible GABAAReceptor Plasticity after Ethanol Intoxication

Mechanisms of Reversible GABAAReceptor Plasticity after Ethanol Intoxication

Effect of isopregnanolone on rapid tolerance to the anxiolytic effect of ethanol

Invertebrate models of drug abuse

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Resources

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Mechanisms of Reversible GABA_AReceptor Plasticity after Ethanol Intoxication

Mechanisms of Reversible GABA_AReceptor Plasticity after Ethanol Intoxication