Chronic Ethanol Administration Alters Immunoreactivity for GABAA Receptor Subunits in Rat Cortex in a Region-Specific Manner

Grobin, A. Chistina; Fritschy, Jean‐Marc; Morrow, A. Leslie

doi:10.1097/00000374-200008000-00002

Cited by 16 publications

(26 citation statements)

References 35 publications

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“…Both mIPSCs and the tonic current show profound tolerance to α1-containing GABA A receptor selective doses of diazepam and zolpidem (Cagetti et al 2003). As previously demonstrated (Grobin et al 2000), chronic EtOH exposure results in a decrease in BZP-sensitive α1-subunits and an increase in BZP-insensitive α4-subunits at synaptic receptors. Thus, THIP (a high affinity and efficacy agonist of the α4-containing GABA A receptors and a partial agonist at most other GABA A receptor assemblies) activated the tonic GABA current in slices from control-untreated rats and had little effect in slices from chronic EtOH exposed rats (Liang et al 2004).…”

Section: Chronic Ethanol Actionssupporting

confidence: 76%

Synaptic Effects Induced by Alcohol

Lovinger

Roberto

2010

Current Topics in Behavioral Neurosciences

125

152

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Ethanol (EtOH) has effects on numerous cellular molecular targets, and alterations in synaptic function are prominent among these effects. Acute exposure to EtOH activates or inhibits the function of proteins involved in synaptic transmission, while chronic exposure often produces opposing and/or compensatory/homeostatic effects on the expression, localization, and function of these proteins. Interactions between different neurotransmitters (e.g., neuropeptide effects on release of small molecule transmitters) can also influence both acute and chronic EtOH actions. Studies in intact animals indicate that the proteins affected by EtOH also play roles in the neural actions of the drug, including acute intoxication, tolerance, dependence, and the seeking and drinking of EtOH. This chapter reviews the literature describing these acute and chronic synaptic effects of EtOH and their relevance for synaptic transmission, plasticity, and behavior.

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Section: Chronic Ethanol Actionssupporting

confidence: 76%

Synaptic Effects Induced by Alcohol

Lovinger

Roberto

2010

Current Topics in Behavioral Neurosciences

125

152

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“…Different brain regions can exhibit different EtOH-induced plastic changes [16, 24]. Therefore, we studied the surface expression of GABA A R subunits α1, α2 α4, γ2 and δ in rat BLA slices 40 days after CIE treatment.…”

Section: Introductionmentioning

confidence: 99%

Ethanol-Induced Plasticity of GABAA Receptors in the Basolateral Amygdala

et al. 2014

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Acute and chronic ethanol (EtOH) administration is known to affect function, surface expression, and subunit composition of γ-aminobutyric acid (A) receptors (GABAARs) in different parts of the brain, which is believed to play a major role in alcohol dependence and withdrawal symptoms. The basolateral amygdala (BLA) participates in anxiety-like behaviors including those induced by alcohol withdrawal. In the present study we assessed the changes in cell surface levels of select GABAAR subunits in the BLA of a rat model of alcohol dependence induced by chronic intermittent EtOH (CIE) treatment and long-term (>40 days) withdrawal and investigated the time-course of such changes after a single dose of EtOH (5 g/kg, gavage). We found an early decrease in surface expression of α4 and γ subunits at 1 h following single dose EtOH treatment. At 48 h post-EtOH and after CIE treatment there was an increase in α4 and γ2, while α1, α2, and γ surface expression were decreased. To relate functional changes in GABAARs to changes in their subunit composition we analyzed miniature inhibitory postsynaptic currents (mIPSCs) and the picrotoxin-sensitive tonic current (Itonic) 48 h after EtOH intoxication. The Itonic magnitude and most of the mIPSC kinetic parameters (except faster mIPSC decay) were unchanged at 48 h post-EtOH. At the same time, Itonic potentiation by acute EtOH was greatly reduced, whereas mIPSCs became significantly more sensitive to potentiation by acute EtOH. These results suggest that EtOH intoxication-induced GABAAR plasticity in the BLA might contribute to the diminished sedative/hypnotic and maintained anxiolytic effectiveness of EtOH.

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“…That a benzodiazepine antagonist with unquestionably clear actions against benzodiazepine agonists shares anxiolytic actions with a benzodiazepine agonist like diazepam seems paradoxical and uncertainty remains as to how flumazenil exerts these effects (Adinoff et al, 1996;Barnard et al, 1998;Britton et al, 1988;Buck et al, 1991;Criswell and Breese, 1993;Little et al, 1985;Moy et al, 1997Moy et al, , 2000. Discussions have focused on c-aminobutyric acid (GABA)-modulatory neuroactive steroid effects, antagonism of endogenous benzodiazepine receptor inverse agonists (which may vary as a function of chronic ethanol exposure) and differential intrinsic activity at benzodiazepine receptor subtypes (see Barnard et al, 1998 for summary), which are known to change their relative abundance as a function of chronic alcohol exposure (e.g., Cagetti et al, 2003;Devaud et al, 1995;Follesa et al, 2003;Grobin et al, 2000). Although the half-life of flumazenil is exceedingly short (16 minutes, Lister et al, 1984;12 to 20 minutes in human brain, Lassen et al, 1995), its actions appear to far outlast its presence (e.g., Knapp et al, 2005).…”

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confidence: 99%