Chronic Ethanol Consumption Differentially Alters GABAA Receptor α1 and α4 Subunit Peptide Expression and GABAA Receptor‐Mediated 36Cl− Uptake in Mesocorticolimbic Regions of Rat Brain

Papadeas, Sophia T.; Grobin, A. Chistina; Morrow, A. Leslie

doi:10.1111/j.1530-0277.2001.tb02347.x

Cited by 59 publications

(42 citation statements)

References 32 publications

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“…Conversely, some data suggest that chronic ethanol consumption may reduce GABAergic function, consistent with the development of tolerance to the acute effects of ethanol (Allan and Harris, 1987;Davis and Wu, 2001). Indeed, adaptations within the GABA system have been suggested to participate in both the development of behavioral tolerance and dependence as well as many aspects of acute and protracted ethanol withdrawal (Grobin et al, 1998;Papadeas et al, 2001;Davies, 2003). Melis et al (2002) reported that a single in vivo injection of ethanol (2 gm/kg, i.p.)…”

Section: Discussionmentioning

confidence: 99%

Increased GABA Release in the Central Amygdala of Ethanol-Dependent Rats

Roberto¹,

Madamba²,

Stouffer³

et al. 2004

J. Neurosci.

267

363

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The central nucleus of amygdala (CeA) is important in regulating alcohol consumption and plays a major role in the anxiogenic response to ethanol withdrawal. We showed previously that acute ethanol augments GABA A receptor-mediated IPSPs and IPSCs, possibly by a presynaptic mechanism. Here, we have examined the interaction of acute ethanol with the GABAergic system in chronic ethanol-treated (CET) rats using an in vitro CeA slice preparation and in vivo brain microdialysis. We found that in CeA slices from CET rats, the baseline evoked IPSP and IPSC amplitudes were increased, and paired-pulse facilitation ratios were lower than in naive rats, suggesting an increased GABAergic transmission after chronic ethanol treatment. Interestingly, acute ethanol (5-66 mM) significantly enhanced IPSPs and IPSCs equally in CET and naive rats, indicating a lack of tolerance for this effect of acute ethanol. Analysis of miniature IPSC frequency suggests that the increased GABAergic transmission by both acute and chronic ethanol arises from a presynaptic mechanism involving enhanced vesicular release of GABA. These data are supported by microdialysis studies showing that CET rats presented a fourfold increase in baseline GABA dialysate content compared with naive rats. In vivo administration of ethanol (0.1, 0.3, and 1.0 M) produced a dose-dependent increase in GABA release in the CeA dialysate in both CET and naive rats. These combined findings suggest that acute and chronic ethanol increases GABA release in CeA and support previous reports that the behavioral actions of ethanol are mediated, in part, by increased GABAergic transmission in the CeA.

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Section: Discussionmentioning

confidence: 99%

Increased GABA Release in the Central Amygdala of Ethanol-Dependent Rats

Roberto¹,

Madamba²,

Stouffer³

et al. 2004

J. Neurosci.

267

363

View full text Add to dashboard Cite

show abstract

“…Likewise, examination of drugs affecting GABA A receptor function implicated differing brain regions for self-administration and ethanol discrimination of ethanol (Hyytia and Koob, 1995;McBride et al, 1999;Roberts et al, 1996;Rodd et al, 2004Rodd et al, , 2005. In further support of a regional specificity of ethanol on GABA transmission, work demonstrated that chronic ethanol treatment altered expression of GABA A receptor subunit mRNAs in some brain regions, but not others Grobin et al, 2000a, b;Montpied et al, 1991;Morrow et al, 1992;Mhatre and Ticku, 1992;Papadeas et al, 2001). electrophysiological recording of spontaneous activity of neurons in anesthetized animals across a variety of brain regions.…”

Section: Regional Specificity Of Ethanol On Functions Altered By Gabamentioning

confidence: 96%

“…After chronic ethanol, an alteration in the expression of a 4 -receptor subunit occurs in some, but not all, brain regions (Grobin et al, 2000a, b;Kumar et al, 2002;Montpied et al, 1991;Papadeas et al, 2001) and the a 6 -receptor subunit is increased in the cerebellum (Mhatre and Ticku, 1992;Morrow et al, 1992). In respect to the increase in the expression of the a 4 -and a 6 -receptor subunits following chronic ethanol exposure, there is often a concomitant downregulation of the a 1 -receptor subunit (Grobin et al, 2000a, b;Mhatre and Ticku, 1992;Morrow et al, 1992;Papadeas et al, 2001).…”

Section: Argument For An Action Of Ethanol On Bzd-insensitive Gaba a mentioning

confidence: 99%

“…In respect to the increase in the expression of the a 4 -and a 6 -receptor subunits following chronic ethanol exposure, there is often a concomitant downregulation of the a 1 -receptor subunit (Grobin et al, 2000a, b;Mhatre and Ticku, 1992;Morrow et al, 1992;Papadeas et al, 2001). While the underlying basis of the shift in these alpha-subunits for GABA A receptors after chronic ethanol is unknown, this change in GABA A receptor subunits is consistent with a close relationship between ethanol action in vivo and GABA function.…”

Section: Argument For An Action Of Ethanol On Bzd-insensitive Gaba a mentioning

confidence: 99%

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A Conceptualization of Integrated Actions of Ethanol Contributing to its GABAmimetic Profile: A Commentary

Criswell

Breese

2005

Neuropsychopharmacol

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Early behavioral investigations supported the contention that systemic ethanol displays a GABAmimetic profile. Microinjection of GABA agonists into brain and in vivo electrophysiological studies implicated a regionally specific action of ethanol on GABA function. While selectivity of ethanol to enhance the effect of GABA was initially attributed an effect on type-1-benzodiazepine (BZD)-GABA A receptors, a lack of ethanol's effect on GABA responsiveness from isolated neurons with this receptor subtype discounted this contention. Nonetheless, subsequent work identified GABA A receptor subtypes, with limited distribution in brain, sensitive to enhancement of GABA at relevant ethanol concentrations. In view of these data, it is hypothesized that the GABAmimetic profile for ethanol is due to activation of mechanisms associated with GABA function, distinct from a direct action on the majority of postsynaptic GABA A receptors. The primary action proposed to account for ethanol's regional specificity on GABA transmission is its ability to release GABA from some, but not all, presynaptic GABAergic terminals. As systemic administration of ethanol increases neuroactive steroids, which can enhance GABA responsiveness, this elevated level of neurosteroids is proposed to magnify the effect of GABA released by ethanol. Additional factors contributing to the degree to which ethanol interacts with GABA function include an involvement of GABA B and other receptors that influence ethanol-induced GABA release, an effect of phosphorylation on GABA responsiveness, and a regional reduction of glutamatergic tone. Thus, an integration of these consequences induced by ethanol is proposed to provide a logical basis for its in vivo GABAmimetic profile.

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“…Moreover mRNA expression of β 1 and γ 2 was reduced in total amygdala samples (Anderson et al, 2007). It has been shown that after 14 days of chronic alcohol consumption there was a decrease of α 1 and α 4 subunit peptide expression in the amygdala, a decrease of α 4 in the NAC but no change in subunit expression in the VTA (Papadeas et al, 2001). …”

Section: Plasticity Of Gaba a Receptor Subunits In Chronic Ethanol Comentioning

confidence: 96%

The role of GABAA receptors in the development of alcoholism

Enoch

2008

Pharmacology Biochemistry and Behavior

197

181

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Alcoholism is a common, heritable, chronic relapsing disorder. GABA A receptors undergo allosteric modulation by ethanol, anesthetics, benzodiazepines and neurosteroids and have been implicated in the acute as well as the chronic effects of ethanol including tolerance, dependence and withdrawal. Medications targeting GABA A receptors ameliorate the symptoms of acute withdrawal. Ethanol induces plasticity in GABA A receptors: tolerance is associated with generally decreased GABA A receptor activation and differentially altered subunit expression. The dopamine (DA) mesolimbic reward pathway originating in the ventral tegmental area (VTA), and interacting stress circuitry play an important role in the development of addiction. VTA GABAergic interneurons are the primary inhibitory regulators of DA neurons and a subset of VTA GABA A receptors may be implicated in the switch from heavy drinking to dependence. GABA A receptors modulate anxiety and response to stress; important elements of sustained drinking and relapse. The GABA A receptor subunit genes clustered on chromosome 4 are highly expressed in the reward pathway. Several recent studies have provided strong evidence that one of these genes, GABRA2, is implicated in alcoholism in humans. The influence of the interaction between ethanol and GABA A receptors in the reward pathway on the development of alcoholism together with genetic and epigenetic vulnerabilities will be explored in this review.

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Chronic Ethanol Consumption Differentially Alters GABA_A Receptor α1 and α4 Subunit Peptide Expression and GABA_A Receptor‐Mediated ³⁶Cl⁻ Uptake in Mesocorticolimbic Regions of Rat Brain

Cited by 59 publications

References 32 publications

Increased GABA Release in the Central Amygdala of Ethanol-Dependent Rats

Increased GABA Release in the Central Amygdala of Ethanol-Dependent Rats

A Conceptualization of Integrated Actions of Ethanol Contributing to its GABAmimetic Profile: A Commentary

The role of GABAA receptors in the development of alcoholism

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