Chronic ethanol and pentobarbital administration in the rat: Effects on GABAA receptor function and expression in brain

Morrow, A. Leslie; Montpied, Pascale; Lingford‐Hughes, Anne; Paul, Steven M.

doi:10.1016/0741-8329(90)90012-2

Cited by 132 publications

(59 citation statements)

References 46 publications

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“…For example, GABAA receptor a1 subunit mRNA levels were significantly decreased following chronic ethanol consumption (Morrow et al, 1990;Montpied et al, 1991;. GABAA receptor a1, a2, and a3 subunit peptide levels were also significantly decreased , whereas GABAA receptor a4 and /32/3 subunit peptide expressions were significantly increased following chronic ethanol consumption (Mhatre and Ticku, 1994;Devaud et al, 1997).…”

Section: Fig 2 Amentioning

confidence: 99%

Differential Regulation of GABA_A Receptor Gene Expression by Ethanol in the Rat Hippocampus Versus Cerebral Cortex

Matthews

Devaud

Fritschy

et al. 1998

Journal of Neurochemistry

103

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Abstract:Previous research has shown that chronic ethanol consumption dramatically alters GABAA receptor a, and a 4 subunit gene expression in the cerebral cortex and GABAA receptor a, and a6 subunit gene expression in the cerebellum. However, it is not yet known if chronic ethanol consumption produces similar alterations in GA-BAA receptor gene expression in other brain regions. One brain region of interest is the hippocampus because it has recently been shown that a subset of GABAA receptors in the hippocampus is responsive to pharmacologically relevant concentrations of ethanol. Therefore, we directly compared the effects of chronic ethanol consumption on GABAA receptor subunit gene expression in the hippocampus and cerebral cortex. Furthermore, we investigated whether the duration of ethanol consumption (14 or 40 days) would influence regulation of GABAA receptor gene expression in these two brain regions. Chronic ethanol consumption produced a significant increase in the level of GABAA receptor a4 subunit peptide in the hippocampus following 40 days but not 14 days. The relative expression of hippocampal GABAA receptor a1, a2, a3, /32/3, or Y2 was not altered by either period of chronic ethanol exposure. In marked contrast, chronic ethanol consumption for 40 days significantly increased the relative expression of cerebral cortical GABAA receptor a4 subunits and significantly decreased the relative expression of cerebral cortical GABAA receptor a, subunits. This finding is consistent with previous results following 14 days of chronic ethanol consumption. Hence, chronic ethanol consumption alters GABAA receptor gene expression in the hippocampus but in a different manner from that in either the cerebral cortex or the cerebellum. Furthermore, these alterations are dependent on the duration of ethanol exposure.

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Section: Fig 2 Amentioning

confidence: 99%

Differential Regulation of GABA_A Receptor Gene Expression by Ethanol in the Rat Hippocampus Versus Cerebral Cortex

Matthews

Devaud

Fritschy

et al. 1998

Journal of Neurochemistry

103

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“…An association between heightened CNS excitability and reduced ␣1 subunit expression has been observed during ontogenic development, alcohol dependence and withdrawal, and in animal models of temporal lobe epilepsy (Aicardi and Chevrie, 1970;Mecarelli et al, 1988;Morrow et al, 1990;Devaud et al, 1997;BrooksKayal et al, 1998;Poulter et al, 1999). Previous studies have suggested various roles for ␣ subunit isoforms in specific BZD-related behaviors (Mohler et al, 1996;Rudolph et al, 1999;Crestani et al, 2000;Low et al, 2000).…”

Section: CLmentioning

confidence: 99%

Molecular and Pharmacological Characterization of GABA_AReceptor α1 Subunit Knockout Mice

Kralic

Korpi

O'Buckley³

et al. 2002

J Pharmacol Exp Ther

184

160

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GABA A receptors mediate fast inhibitory neurotransmission in the central nervous system (CNS), and approximately half of these receptors contain ␣1 subunits. GABA A receptor ␣1 subunits are important for receptor assembly and specific pharmacological responses to benzodiazepines. Plasticity in GABA A receptor ␣1 subunit expression is associated with changes in CNS excitability observed during normal brain development, in animal models of epilepsy, and upon withdrawal from alcohol and benzodiazepines. To examine the role of ␣1 subunitcontaining GABA A receptors in vivo, we characterized receptor subunit expression and pharmacological properties in cerebral cortex of knockout mice with a targeted deletion of the ␣1 subunit. The mice are viable but exhibit an intention tremor. Western blot analysis confirms the complete loss of ␣1 subunit peptide expression. Stable adaptations in the expression of several GABA A receptor subunits are observed in the fifth to seventh generations, including decreased expression of ␤2/3 and ␥2 subunits and increased expression of ␣2 and ␣3 subunits. There was no change in ␣4, ␣5, or ␦ subunit peptide levels in cerebral cortex. Knockout mice exhibit loss of over half of GABA A receptors measured by [ 3

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“…The latter effect was proposed to result from channel block due to steroid binding to yet another site, distinct from those involved in potentiation or the type of inhibition produced by pregnenolone sulfate. Also, Morrow et al (Morrow et al, 1990) found that the potentiation curves of muscimol-stimulated chloride uptake into rat brain synaptosomes were biphasic for many steroids suggesting that steroid interactions with multiple binding sites underlie their effects on the receptor, and others have found biphasic effects of 5β-reduced potentiating steroids on TBPS binding (Hawkinson et al, 1994). However, the caveat to these findings is that several subtypes of GABA A receptors, each with their own distinct pharmacological properties, could exist in the synaptoneurosome preparation used.…”

Section: B Multiple Sites For Steroids -Pharmacological and Moleculmentioning

confidence: 99%

Mechanisms of neurosteroid interactions with GABAA receptors

Akk¹,

Covey²,

Evers³

et al. 2007

Pharmacology & Therapeutics

147

166

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Neuroactive steroids have some of their most potent actions by augmenting the function of GABA A receptors. Endogenous steroid actions on GABA A receptors may underlie important effects on mood and behavior. Exogenous neuroactive steroids have potential as anesthetics, anticonvulsants, and neuroprotectants. We have taken multiple approaches to understand more completely the interaction of neuroactive steroids with GABA A receptors. We have developed many novel steroid analogues in this effort. Recent work has resulted in synthesis of new enantiomer analogue pairs, novel ligands that probe various properties of the steroid pharmacophore, fluorescent neuroactive steroid analogues, and photoaffinity labels. Using these tools, combined with receptor binding and electrophysiological assays, we have begun to untangle the complexity of steroid actions at this important class of ligand-gated ion channel.

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Chronic ethanol and pentobarbital administration in the rat: Effects on GABAA receptor function and expression in brain

Cited by 132 publications

References 46 publications

Differential Regulation of GABA_A Receptor Gene Expression by Ethanol in the Rat Hippocampus Versus Cerebral Cortex

Differential Regulation of GABA_A Receptor Gene Expression by Ethanol in the Rat Hippocampus Versus Cerebral Cortex

Molecular and Pharmacological Characterization of GABA_AReceptor α1 Subunit Knockout Mice

Mechanisms of neurosteroid interactions with GABAA receptors

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Chronic ethanol and pentobarbital administration in the rat: Effects on GABAA receptor function and expression in brain

Cited by 132 publications

References 46 publications

Differential Regulation of GABAA Receptor Gene Expression by Ethanol in the Rat Hippocampus Versus Cerebral Cortex

Differential Regulation of GABAA Receptor Gene Expression by Ethanol in the Rat Hippocampus Versus Cerebral Cortex

Molecular and Pharmacological Characterization of GABAAReceptor α1 Subunit Knockout Mice

Mechanisms of neurosteroid interactions with GABAA receptors

Contact Info

Product

Resources

About

Differential Regulation of GABA_A Receptor Gene Expression by Ethanol in the Rat Hippocampus Versus Cerebral Cortex

Differential Regulation of GABA_A Receptor Gene Expression by Ethanol in the Rat Hippocampus Versus Cerebral Cortex

Molecular and Pharmacological Characterization of GABA_AReceptor α1 Subunit Knockout Mice