Expression of specific ionotropic glutamate and GABA-A receptor subunits is decreased in central amygdala of alcoholics

Jin, Zhe; Bhandage, Amol K.; Bazov, Igor; Кононенко, О.; Bakalkin, Georgy; Korpi, Esa R.; Birnir, Bryndis

doi:10.3389/fncel.2014.00288

Cited by 32 publications

(33 citation statements)

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“…In agreement with the macaque data, down‐regulation of α2 mRNA has also been found post‐mortem in alcoholic patients (Jin et al . ); of 19 GABA A receptor subunits investigated in the central nucleus of the amygdala, only the mRNA encoding the α2 subunit was significantly down‐regulated in alcoholic patients compared with control subjects, though in the human cohort, it is not possible to deduce whether the lowered expression was present prior to onset of alcohol abuse.…”

Section: Evidence For Gabaa Receptor Involvement In Addictionmentioning

confidence: 99%

GABA_A receptor subtype involvement in addictive behaviour

Stephens

King

Lambert

et al. 2016

Genes Brain and Behavior

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GABA A receptors form the major class of inhibitory neurotransmitter receptors in the mammalian brain. This review sets out to summarize the evidence that variations in genes encoding GABA A receptor isoforms are associated with aspects of addictive behaviour in humans, while animal models of addictive behaviour also implicate certain subtypes of GABA A receptor. In addition to outlining the evidence for the involvement of specific subtypes in addiction, we summarize the particular contributions of these isoforms in control over the functioning of brain circuits, especially the mesolimbic system, and make a first attempt to bring together evidence from several fields to understanding potential involvement of GABA A receptor subtypes in addictive behaviour. While the weight of the published literature is on alcohol dependency, the underlying principles outlined are relevant across a number of different aspects of addictive behaviour.Keywords: Alcohol, animal model, benzodiazepine, conduct disorder, electrophysiology, gene association, gene knockout, impulsivity, nucleus accumbens, psychostimulant, reward Received 31 May 2016, revised 19 July 2016, accepted for publication 15 August 2016Both human and animal studies have implicated GABA A receptors in addiction processes. This article sets out to review the evidence for GABA A receptor involvement in relation to alcoholism and addiction to other drugs of abuse. It will begin with a summary of the structure and function of GABA A receptors and their subtype diversity, before reviewing the human and animal literature providing genetic and behavioural evidence for the role of GABA A receptors in addictive behaviour. Finally, we will attempt to integrate these data into our understanding of addiction processes, and their underlying neurobiology. While the review concerns itself broadly with GABAergic systems and addictive behaviour, the weight of the published literature is on alcohol dependency. Nevertheless, the underlying principles outlined are relevant across a number of different aspects of addictive behaviour.

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Section: Evidence For Gabaa Receptor Involvement In Addictionmentioning

confidence: 99%

GABA_A receptor subtype involvement in addictive behaviour

Stephens

King

Lambert

et al. 2016

Genes Brain and Behavior

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“…In fact, withdrawal from alcohol is associated with increased glutamate concentration in both humans and rodents (Hermann et al, 2012) and severity of alcohol dependence is positively correlated with CSF glutamate (Umhau et al, 2010). Furthermore, a growing body of literature is emerging indicating that significant glutamatergic adaptations occur in brain regions underlying reward, cognition, and affect in alcohol-dependent individuals (Jin et al, 2014a, 2014b; Enoch et al, 2014; Bhandage et al, 2014; Laukkanen et al, 2015). While human studies are critical to our understanding of the neuroadaptive processes that occur in addicted individuals, animal models have been essential to our appreciation of the cellular adaptations that occur within the neural circuits underlying dependence-induced symptomology, which may help to uncover pharmacological targets for the treatment of alcoholism.…”

Section: Overview Of Glutamate Receptorsmentioning

confidence: 99%

Glutamatergic plasticity and alcohol dependence-induced alterations in reward, affect and cognition

Burnett

Chandler

Trantham-Davidson

2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Introduction Alcohol dependence is characterized by a reduction in reward threshold, development of a negative affective state, and significant cognitive impairments. Dependence-induced glutamatergic neuroadaptations in the neurocircuitry mediating reward, affect and cognitive function are thought to underlie the neural mechanism for these alterations. These changes serve to promote increased craving for alcohol and facilitate the development of maladaptive behaviors that promote relapse to alcohol drinking during periods of abstinence. Objective To review the extant literature on the effects of chronic alcohol exposure on glutamatergic neurotransmission and its impact on reward, affect and cognition. Results Evidence from a diverse set of studies demonstrates significant enhancement of glutamatergic activity following chronic alcohol exposure and up-regulation of GluN2B-containing NMDA receptor expression and function is a commonly observed phenomenon that likely reflects activity-dependent adaptive homeostatic plasticity. However, changes in NMDA receptors and additional glutamatergic neuroadaptations are often circuit and cell-type specific. Discussion Dependence-induced alterations in glutamate signaling contribute to many of the symptoms experienced in addicted individuals and can persist well into abstinence. This suggests they play an important role in the development of behaviors that increase the probability for relapse. As our understanding of the complexity of the neurocircuitry involved in the addictive process has advanced, it has become increasingly clear that investigations of cell-type and circuit-specific effects are required to gain a more comprehensive understanding of the glutamatergic adaptations and their functional consequences in alcohol addiction. Conclusion While pharmacological treatments for alcohol dependence and relapse targeting the glutamatergic system have shown great promise in preclinical models, more research is needed to uncover novel, possibly circuit-specific, targets with improved efficacy and reduced side effects.

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“…The relative quantification of gene expression was performed using 2 -△Ct method [△Ct=Ct target gene -Ct reference gene ] (Jin et al, 2014). Data were statistically analyzed using Microsoft Excel and SPSS 16.0 software, and the relative expression was presented as means±SEM.…”

Section: Data Processingmentioning

confidence: 99%

Effect of Heat Stress on the Expression of GABA Receptor mRNA in the HPG Axis of Wenchang Chickens

Xie

et al. 2016

Rev. Bras. Cienc. Avic.

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We investigated the effect of heat stress (HS) on the expression of the GABA receptor in the hypothalamic-pituitary-gonadal (HPG) axis of Wenchang chickens. Real-time quantitative RT-PCR (qRT-PCR) was used to quantify the GABA receptor mRNA levels along the HPG axis of chickens under HS (40±0.5 °C) for 1-6 weeks. Our results showed that the expression of GABA A and GABA B receptor at the mRNAs levels in the tissues of HPG axis exhibited fluctuation and variability. After HS, the mRNA level of GABA A receptor was significantly reduced in the hypothalamus of 1-week-old and in the pituitary of 3-week-old chickens, but significantly increased in the pituitary of 1-, 4-, and 5-weekold chickens. The GABA B receptor mRNA level significantly declined in the hypothalamus of 1-week-old and in the pituitary of 3-week-old chickens, but was significantly upregulated in the pituitary and testis of 1-and 2-week-old chickens. At other time points, the expressions of GABA A receptor and GABA B receptor showed no significant differences compared with control group. These results indicated that the levels of GABA A receptor and GABA B receptor mRNAs varied in different tissues of the HPG axis in chickens of different ages, displaying temporal and spatial variations. GABA receptor behaved as a positively-regulated gene by HS, i.e., its mRNA was increased by HS; similarly, it was a negativelyregulated gene by HS, when its expression was reduced by HS.

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Expression of specific ionotropic glutamate and GABA-A receptor subunits is decreased in central amygdala of alcoholics

Cited by 32 publications

References 64 publications

GABA_A receptor subtype involvement in addictive behaviour

GABA_A receptor subtype involvement in addictive behaviour

Glutamatergic plasticity and alcohol dependence-induced alterations in reward, affect and cognition

Effect of Heat Stress on the Expression of GABA Receptor mRNA in the HPG Axis of Wenchang Chickens

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Expression of specific ionotropic glutamate and GABA-A receptor subunits is decreased in central amygdala of alcoholics

Cited by 32 publications

References 64 publications

GABAA receptor subtype involvement in addictive behaviour

GABAA receptor subtype involvement in addictive behaviour

Glutamatergic plasticity and alcohol dependence-induced alterations in reward, affect and cognition

Effect of Heat Stress on the Expression of GABA Receptor mRNA in the HPG Axis of Wenchang Chickens

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GABA_A receptor subtype involvement in addictive behaviour

GABA_A receptor subtype involvement in addictive behaviour