Ethanol affects limbic and striatal presynaptic glutamatergic and DNA methylation gene expression in outbred rats exposed to early‐life stress

Vrettou, Maria; Granholm, Linnea; Todkar, Aniruddha; Nilsson, Kent W.; Wallén-Mackenzie, Åsa; Nylander, Ingrid; Comasco, Erika

doi:10.1111/adb.12331

Cited by 19 publications

(51 citation statements)

References 49 publications

(72 reference statements)

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“…Alcohol intake data have been previously reported [ 30 , 36 , 37 ]. The MS15 and MS360 groups did not differ in alcohol consumption although the propensity to increase alcohol intake over time and consume >1.5 g/kg/2 h was more evident in the MS360 group [ 37 ], as also reported in several studies [ 38 ].…”

Section: Resultsmentioning

confidence: 99%

Evidence for a Link Between Fkbp5/FKBP5, Early Life Social Relations and Alcohol Drinking in Young Adult Rats and Humans

et al. 2016

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Alcohol misuse has been linked to dysregulation of stress, emotion, and reward brain circuitries. A candidate key mediator of this association is the FK506-binding protein (FKBP5), a negative regulator of the glucocorticoid receptor. The aim of the present study was to further understand the Fkbp5/FKBP5-related genetic underpinnings underlying the relationship between early life social relations and alcohol drinking. The effect of maternal separation and voluntary alcohol drinking on Fkbp5 expression was investigated in the brain of young adult rats, whereas the interaction effect of the functional FKBP5 single nucleotide polymorphism rs1360780 genotype and parent-child relationship on problematic drinking was examined in young adult humans. In rats, Fkbp5 expression in the nucleus accumbens and ventral tegmental area, core regions of the reward system, was affected in a region-dependent manner and in opposite direction by maternal separation and alcohol drinking. Fkbp5 expression in the cingulate cortex was affected by the combined effect of maternal separation and alcohol drinking. In humans, the TT genotype, in the presence of a poor relationship between the child and parents, was associated with problematic drinking behavior. The present findings suggest that Fkbp5 expression in mesocorticolimbic dopaminergic regions associates with early life stress-mediated sensitivity to alcohol drinking and that FKBP5 genotype interacts with parent-child relationship to influence alcohol drinking. These findings are the first to point to a role of FKBP5 in propensity to alcohol misuse and call for studies of the underlying molecular mechanisms to identify potential drug targets.Electronic supplementary materialThe online version of this article (doi:10.1007/s12035-016-0157-z) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Evidence for a Link Between Fkbp5/FKBP5, Early Life Social Relations and Alcohol Drinking in Young Adult Rats and Humans

et al. 2016

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“…Furthermore, genetic vulnerability to alcohol use disorders involves alterations in the glutamatergic system, including those involving VGLUT2 expression and function [25,106]. Indeed, VGLUT2 expression changes in ethanol-consuming rats that were previously exposed to early-life stress [107]. Moreover, chronic stress leads to altered expression of glutamatergic receptors in the NAcSh and increases both the locomotor activating effects and motivation for alcohol.…”

Section: Alcoholmentioning

confidence: 99%

Roles of dopamine and glutamate co‐release in the nucleus accumbens in mediating the actions of drugs of abuse

et al. 2020

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Projections of ventral tegmental area dopamine (DA) neurons to the medial shell of the nucleus accumbens have been increasingly implicated as integral to the behavioral and physiological changes involved in the development of substance use disorders (SUDs). Recently, many of these nucleus accumbens-projecting DA neurons were found to also release the neurotransmitter glutamate. This glutamate co-release from DA neurons is critical in mediating the effect of drugs of abuse on addiction-related behaviors. Potential mechanisms underlying the role(s) of dopamine/glutamate co-release in contributing to SUDs are unclear. Nevertheless, an important clue may relate to glutamate's ability to potentiate loading of DA into synaptic vesicles within terminals in the nucleus accumbens in response to drug-induced elevations in neuronal activity, enabling a more robust release of DA after stimulation. Here, we summarize how drugs of abuse, particularly cocaine, opioids, and alcohol, alter DA release in the nucleus accumbens medial shell, examine the potential role of DA/glutamate co-release in mediating these effects, and discuss future directions for further investigating these mechanisms.

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“…Long-term changes in DNMT1 and MeCP2 were negatively correlated to the voluntary drinking behavior of these rats (Vrettou et al, 2015). Long-term alterations of DNMT1 were also observed in the offspring of animals stressed during pregnancy, which demonstrated behavioral abnormalities similar to what has been observed in schizophrenic patients during adulthood.…”

Section: Epigenetics and Stress-related Disordersmentioning

confidence: 99%

Epigenetic mechanisms of alcoholism and stress-related disorders

Palmisano

Pandey

2017

Alcohol

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Stress-related disorders, such as anxiety, early life stress and posttraumatic stress disorder appear to be important factors in promoting alcoholism, as alcohol consumption can temporarily attenuate the negative affective symptoms of these disorders. Several molecules involved in signaling pathways may contribute to the neuroadaptation induced during alcohol dependence and stress disorders, and among these, brain-derived neurotrophic factor (BDNF), corticotropin releasing factor (CRF), neuropeptide Y (NPY) and opioid peptides (i.e. nociceptin and dynorphin) are involved in the interaction of stress and alcohol. In fact, alterations in the expression and function of these molecules have been associated with the pathophysiology of stress-related disorders and alcoholism. In recent years, various studies have focused on the epigenetic mechanisms that regulate chromatin architecture thereby modifying gene expression. Interestingly, epigenetic modifications in specific brain regions have been shown to be associated with the neurobiology of psychiatric disorders, including alcoholism and stress. In particular, the enzymes responsible for chromatin remodeling (i.e. histone deacetylases and methyltransferases, DNA methyltransferases) have been identified as common molecular mechanisms for the interaction of stress and alcohol and have become promising therapeutic targets to treat or prevent alcoholism and associated emotional disorders.

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Ethanol affects limbic and striatal presynaptic glutamatergic and DNA methylation gene expression in outbred rats exposed to early‐life stress

Cited by 19 publications

References 49 publications

Evidence for a Link Between Fkbp5/FKBP5, Early Life Social Relations and Alcohol Drinking in Young Adult Rats and Humans

Evidence for a Link Between Fkbp5/FKBP5, Early Life Social Relations and Alcohol Drinking in Young Adult Rats and Humans

Roles of dopamine and glutamate co‐release in the nucleus accumbens in mediating the actions of drugs of abuse

Epigenetic mechanisms of alcoholism and stress-related disorders

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