Persistent reduction of GABAA receptor-mediated inhibition in rat hippocampus after chronic intermittent ethanol treatment

Kang, Maeng-Hee; Spigelman, Igor; Sapp, Douglas W.; Olsen, Richard W.

doi:10.1016/0006-8993(95)01274-5

Cited by 96 publications

(85 citation statements)

References 33 publications

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“…In the chronic intermittent ethanol (CIE) model of ethanol dependence in the rat, multiple withdrawal cycles of ethanol result in a kindling effect to increase seizure susceptibility, increase anxiety and produce insomnia, as well as promote self-administration (Olsen et al, 2005). This hyperexcitability state is a result of decreased hippocampal circuit excitability as evidenced by decreases in paired pulse inhibition (Kang et al, 1996). Increased α4 expression was found in the CIE model across multiple regions of the hippocampal formation, including dentate gyrus, CA3 and CA1 (Mahmoudi et al, 1997).…”

Section: Ethanolmentioning

confidence: 99%

Neurosteroid regulation of GABAA receptors: Focus on the α4 and δ subunits

Smith

Shen

Gong

et al. 2007

Pharmacology & Therapeutics

217

197

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Neurosteroids, such as the progesterone metabolite 3α-OH-5α[β]-pregnan-20-one (THP or [allo] pregnanolone), function as potent positive modulators of the GABA A receptor (GABAR) when acutely administered. However, fluctuations in the circulating levels of this steroid at puberty, across endogenous ovarian cycles, during pregnancy or following chronic stress produce periods of prolonged exposure and withdrawal, where changes in GABAR subunit composition may occur as compensatory responses to sustained levels of inhibition. A number of laboratories have demonstrated that both chronic administration of THP as well as its withdrawal transiently increase expression of the α4 subunit of the GABAR in several areas of the central nervous system (CNS) as well as in in vitro neuronal systems. Receptors containing this subunit are insensitive to benzodiazepine (BDZ) modulation and display faster deactivation kinetics, which studies suggest underlie hyperexcitability states. Similar increases in α4 expression are triggered by withdrawal from other GABA-modulatory compounds, such as ethanol and BDZ, suggesting a common mechanism. Other studies have reported puberty or estrous cycle-associated increases in δ-GABAR, the most sensitive target of these steroids which underlies a tonic inhibitory current. In the studies reported here, the effect of steroids on inhibition, which influence anxiety state and seizure susceptibility, depend not only on the subunit composition of the receptor but also on the direction of Cl -current generated by these target receptors. The effect of neurosteroids on GABAR function thus results in behavioral outcomes relevant for pubertal mood swings, premenstrual dysphoric disorder and catamenial epilepsy, which are due to fluctuations in endogenous steroids.

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Section: Ethanolmentioning

confidence: 99%

Neurosteroid regulation of GABAA receptors: Focus on the α4 and δ subunits

Smith

Shen

Gong

et al. 2007

Pharmacology & Therapeutics

217

197

View full text Add to dashboard Cite

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“…However, because of the recent findings showing that hippocampal GABAA receptors are, in fact, responsive to ethanol (Weiner et al, 1994(Weiner et al, , 1997aWan et al, 1996), research has begun focusing on the effect of chronic ethanol consumption on hippocampal GABAA receptor gene expression. In a chronic intermittent ethanol paradigm, a procedure in which animals undergo at least 60 ethanol withdrawal periods, GABAA receptor-mediated Cl flux was reduced (Kang et al, 1996), and GABAA receptor a4 subunit mRNA level was significantly increased in the hippocampus (Mahmoudi et al, 1997). Furthermore, hippocampal GABAA a1 subunit peptide expression was decreased following 12 weeks of chronic ethanol consumption but was not decreased following 1, 2, or 4 weeks of chronic ethanol consumption (Chariton et al, 1997).…”

mentioning

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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“…Thus, the tolerance of LAMG neuronal firing to the first dose of binge ethanol observed in the present study may be related to adaptive changes of NMDA receptors induced by CIE administration. It has been observed that chronic ethanol treatment also reduces the action of GABA (Kang et al, 1996;Faingold et al, 1998), which may involve GABA A receptor subunit alterations in the brain including the amygdala (Devaud et al, 1995;Grobin et al, 2000;Floyd et al, 2004;Liang et al, 2006). Therefore, a decrease in GABA A receptor function may also contribute to the tolerance of LAMG neuronal firing to ethanol following CIE administration.…”

Section: Discussionmentioning

confidence: 99%

The effects of chronic ethanol administration on amygdala neuronal firing and ethanol withdrawal seizures

Feng

Faingold

2008

Neuropharmacology

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SummaryPhysical dependence on ethanol results in an ethanol withdrawal (ETX) syndrome including susceptibility to audiogenic seizures (AGS) in rodents after abrupt cessation of ethanol. Chronic ethanol administration and ETX induce functional changes of neurons in several brain regions, including the amygdala. Amygdala neurons are requisite elements of the neuronal network subserving AGS propagation during ETX induced by a subacute "binge" ethanol administration protocol. However, the effects of chronic ethanol administration on amygdala neuronal firing and ETX seizure behaviors are unknown. In the present study ethanol (5 g/kg) was administered intragastrically in Sprague-Dawley rats once daily for 28 days [chronic intermittent ethanol (CIE) protocol]. One week later the rats began receiving ethanol intragastrically 3 times daily for 4 days (binge protocol). Microwire electrodes were implanted prior to CIE or on the day after CIE ended day 29 to record extracellular action potentials in lateral amygdala (LAMG) neurons. The first dose of ethanol administered in the binge protocol following CIE treatment did not alter LAMG neuronal firing, which contrasts with firing suppression seen previously in the binge protocol alone. These data indicate that CIE induces neuroadaptive changes in the ETX network which reduce LAMG response to ethanol. LAMG neuronal responses to acoustic stimuli prior to AGS were significantly decreased during ETX as compared to those before ethanol treatment. LAMG neurons fired tonically throughout the tonic convulsions during AGS. CIE plus binge treatment resulted in a significantly greater mean seizure duration and a significantly elevated incidence of death than was seen previously with the binge protocol alone, indicating an elevated seizure severity following chronic ethanol administration.

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Persistent reduction of GABAA receptor-mediated inhibition in rat hippocampus after chronic intermittent ethanol treatment

Cited by 96 publications

References 33 publications

Neurosteroid regulation of GABAA receptors: Focus on the α4 and δ subunits

Neurosteroid regulation of GABAA receptors: Focus on the α4 and δ subunits

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

The effects of chronic ethanol administration on amygdala neuronal firing and ethanol withdrawal seizures

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Persistent reduction of GABAA receptor-mediated inhibition in rat hippocampus after chronic intermittent ethanol treatment

Cited by 96 publications

References 33 publications

Neurosteroid regulation of GABAA receptors: Focus on the α4 and δ subunits

Neurosteroid regulation of GABAA receptors: Focus on the α4 and δ subunits

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

The effects of chronic ethanol administration on amygdala neuronal firing and ethanol withdrawal seizures

Contact Info

Product

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