Alcohol and Developing Neuronal Circuits

Valenzuela, C. Fernando; Morton, Russell A.

doi:10.1016/b978-0-12-405941-2.00007-9

Cited by 4 publications

(5 citation statements)

References 193 publications

(222 reference statements)

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“…However, this was the result of a study on acute alcohol intake that can be considered a physiological effect of moderate alcohol consumption. This contrasts with the decrease in inhibitory neurotransmitters and poor functional connectivity of the brain observed in chronic drinkers [6,7]. Heavy drinkers have lower functional connectivity in the visual and frontal cortices, default mode network, and thalamus, and the cerebellum showed higher functional connections compared with the control group according to resting-state functional MRI study [8].…”

Section: Introductionmentioning

confidence: 81%

Graph Theoretical Analysis of Brain Structural Connectivity in Patients with Alcohol Dependence

Lee,

Jung,

Chung

et al. 2023

Exp Neurobiol

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This study aimed to compare brain structural connectivity using graph theory between patients with alcohol dependence and social drinkers. The participants were divided into two groups; the alcohol group (N=23) consisting of patients who had been hospitalized and had abstained from alcohol for at least three months and the control group (N=22) recruited through advertisements and were social drinkers. All participants were evaluated using 3T magnetic resonance imaging. A total of 1000 repeated whole-brain tractographies with random parameters were performed using DSI Studio. Four hundred functionally defined cortical regions of interest (ROIs) were parcellated using FreeSurfer based on the Schaefer Atlas. The ROIs were overlaid on the tractography results to generate 1000 structural connectivity matrices per person, and 1000 matrices were averaged into a single matrix per subject. Graph analysis was performed through igraph R package. Graph measures were compared between the two groups using analysis of covariance, considering the effects of age and smoking pack years. The alcohol group showed lower local efficiency than the control group in the whole-brain (F=5.824, p=0.020), somato-motor (F=5.963, p=0.019), and default mode networks (F=4.422, p=0.042). The alcohol group showed a lower global efficiency (F=5.736, p=0.021) in the control network. The transitivity of the alcohol group in the dorsal attention network was higher than that of the control (F=4.257, p=0.046). Our results imply that structural stability of the whole-brain network is affected in patients with alcohol dependence, which can lead to ineffective information processing in cases of local node failure.

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Section: Introductionmentioning

confidence: 81%

Graph Theoretical Analysis of Brain Structural Connectivity in Patients with Alcohol Dependence

Lee,

Jung,

Chung

et al. 2023

Exp Neurobiol

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“…During subsequent periods of alcohol withdrawal, the compensatory decrease in GABA relative to glutamate causes excitotoxicity, which may partially account for alcohol-related brain damage. 30 This may imply that similar effects are likely seen with other GABAergic medications, such as chronic benzodiazepine use (Figure 3).…”

Section: The Role Of Gaba In Neuroinflammationmentioning

confidence: 89%

“…GABA is the main inhibitory neurotransmitter in the brain. 30 In astrocytes, glutamate is used as the precursor for GABA production and, as such, the two are in chemical equilibrium in the normal steady state. 31 When glutamate levels rise endogenously, GABA also necessarily increases following Le Chatelier principle.…”

Section: The Role Of Gaba In Neuroinflammationmentioning

confidence: 99%

The roles of neuroinflammation and glutamatergic excitotoxicity in treatment-resistant depression

Candee

Wilkenson

Schreiber

et al. 2023

Jaapa

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Major depressive disorder affects nearly 20% of people during their lifetime. A growing body of evidence supports the theory that neuroinflammation plays a prominent role in the neurobiology of depression, which implicates glutamate and gamma aminobutyric acid as key factors in the pathophysiology of the disease process. This article reviews the pathologic pathways of glutamate excess in the central nervous system and how they may be implicated in the underlying disorder of treatment-resistant depression and targeted for treatment.

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“…Alcohol exerts its effect in the brain by interacting with multiple neurocircuits (Valenzuela, 1997), especially disrupting the delicate balance between γ‐aminobutyric acid (GABA), the primary inhibitory neurotransmitter, and glutamate, the primary excitatory neurotransmitter in the brain. Many studies have established that alcohol‐induced alterations in GABAergic transmission are associated with the development of addiction in rodent models (for review, see Olsen & Liang, 2017).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological administration of 3α,5α‐THP into the nucleus accumbens core increases 3α,5α‐THP expression and reduces alcohol self‐administration

Ornelas

Boero

Voorhies

et al. 2023

Alcohol: Clinical and Experimental Research

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Background: Alcohol affects multiple circuits in the brain, mainly disrupting the delicate balance between inhibitory γ-aminobutyric acid (GABA) transmission and excitatory glutamate signaling in brain areas involved in reward circuits. These include the amygdala, nucleus accumbens (Acb), and ventral tegmental area (VTA). This action impairs circuits that regulate behavioral control of craving and alcohol seeking and intake. Studies in both rodent models and postmortem human brain of patients with alcohol use disorder (AUD) have highlighted the association between the loss of GABAergic inhibition and the development of addiction. The neurosteroid (3α,5α)-3hydroxypregnan-20-one (3α,5α-THP) is a potent positive modulator of GABA A receptors. Chronic alcohol consumption reduces 3α,5α-THP levels, resulting in decreased GABA inhibition. We previously demonstrated that enhancing neurosteroid biosynthesis by overexpression of the cholesterol side-chain cleavage enzyme P450scc decreased alcohol intake in male alcohol-preferring rats (P-rats). While most of the evidence of alcohol-induced alterations comes from studies in male subjects, some data show that females are more vulnerable to alcohol's effects than males. Methods:In this study, we investigated the ability of 3α,5α-THP direct infusions in two brain regions that contribute to alcohol reinforcement, the VTA and Acb core (AcbC), to regulate alcohol self-administration in female P-rats.Results: Administration of 3α,5α-THP into the AcbC increased 3α,5α-THP-positive cell expression in this area and reduced alcohol self-administration. By contrast, 3α,5α-THP infusion into the VTA did not significantly affect alcohol self-administration, though trends for a reduction were found. Conclusions:Our results show that local increases in 3α,5α-THP in the AcbC may alter mesolimbic activity that drives a reduction in alcohol self-administration.

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Alcohol and Developing Neuronal Circuits

Cited by 4 publications

References 193 publications

Graph Theoretical Analysis of Brain Structural Connectivity in Patients with Alcohol Dependence

Graph Theoretical Analysis of Brain Structural Connectivity in Patients with Alcohol Dependence

The roles of neuroinflammation and glutamatergic excitotoxicity in treatment-resistant depression

Pharmacological administration of 3α,5α‐THP into the nucleus accumbens core increases 3α,5α‐THP expression and reduces alcohol self‐administration

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