Epigenetics and addiction

Cadet, Jean Lud; McCoy, Michael T.; Jayanthi, Subramaniam

doi:10.1002/cpt.345

Cited by 27 publications

(17 citation statements)

References 76 publications

(184 reference statements)

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“…Class I HDACs are known regulators of gene expression [13]. Several laboratories have implicated a role of some of these enzymes in the process of addiction to several drugs of abuse including cocaine, amphetamine, and METH [20,21,22,23,24]. The present study documented higher expression of HDAC1, HDAC3, and HDAC8 in SS in comparison to SR, suggesting that the changes in the expression of these enzymes may be associated with the abstinent state.…”

Section: Discussionsupporting

confidence: 61%

Differential Expression of mRNAs Coding for Histone Deacetylases (HDACs) in the Nucleus Accumbens of Compulsive Methamphetamine Takers and Abstinent Rats

Cadet¹,

Ladenheim²,

Krasnova³

et al. 2016

J Drug Alcohol Res

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Methamphetamine (METH) addiction is a common neuropsychiatric disorder that is associated with loss of control over drug use. The long-term manifestations of METH addiction may be related to epigenetic neuroadaptations in the brain. To test this idea, we used rats of divergent phenotypes triggered by footshocks that helped to distinguish rats that continue to take METH compulsively (shockresistant, SR) from those that become abstinent (shock-sensitive, SS). Male Sprague-Dawley rats were trained to self-administer METH (0.1 mg/kg/injection, IV) or saline during twenty 9-hour sessions. During training, all rats escalated their intake of METH. Following the training phase, rats were subjected to progressive increases in footshock intensity. This approach led to a split of the rats into the SR and SS phenotypes. Two hours after the last shock sessions the nucleus accumbens (NAc) was dissected and processed to measure mRNA levels. We found significant differences in the expression of HDAC1, HDAC3, HDAC6, and HDAC8 between the SR and SS rats. There was also increased expression of HDAC11 in the SS group in comparison to the SR and control groups. There were also significant differences in the mRNA expression of Sirt1, Sirt2, Sirt3, Sirt5, Sirt6, and Sirt7, with Sirt2 showing the greatest increase in the SS phenotype. Because these HDACs are differentially located in the cytoplasm, mitochondria, and the nucleus, these results suggest that METH self-administration may have impacted signaling pathways in various cellular compartments. Further dissection of these pathways should help us to elucidate molecular events that are involved in the maintenance of abstinence.

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Section: Discussionsupporting

confidence: 61%

Differential Expression of mRNAs Coding for Histone Deacetylases (HDACs) in the Nucleus Accumbens of Compulsive Methamphetamine Takers and Abstinent Rats

Cadet¹,

Ladenheim²,

Krasnova³

et al. 2016

J Drug Alcohol Res

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“…Given this potential, studies have pursued epigenetic measurement in epidemiologic and clinical studies, as summarized in recent reviews specific to autism spectrum disorder [11], bipolar disorder [12], schizophrenia [13, 14], post-traumatic stress disorder [15], substance abuse disorder [16], and other neuropsychiatric disorders. Epigenetic marks are being investigated for their potential mechanistic disease role as either a mediator or a modifier of environmental or genetic risk, or as a biomarker of exposure or disease (Fig.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Research in Neuropsychiatric Disorders: the “Tissue Issue”

Bakulski

Halladay

et al. 2016

Curr Behav Neurosci Rep

119

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Purpose of Review Evidence has linked neuropsychiatric disorders with epigenetic marks as either a biomarker of disease, biomarker of exposure, or mechanism of disease processes. Neuropsychiatric epidemiologic studies using either target brain tissue or surrogate blood tissue each have methodological challenges and distinct advantages. Recent findings Brain tissue studies are challenged by small sample sizes of cases and controls, incomplete phenotyping, post-mortem timing, and cellular heterogeneity, but the use of a primary disease relevant tissue is critical. Blood-based studies have access to much larger sample sizes and more replication opportunities, as well as the potential for longitudinal measurements, both prior to onset and during the course of treatments. Yet, blood studies also are challenged by cell-type heterogeneity, and many question the validity of using peripheral tissues as a brain biomarker. Emerging evidence suggests that these limitations to blood-based epigenetic studies are surmountable, but confirmation in target tissue remains important. Summary Epigenetic mechanisms have the potential to help elucidate biology connecting experiential risk factors with neuropsychiatric disease manifestation. Cross-tissue studies as well as advanced epidemiologic methods should be employed to more effectively conduct neuropsychiatric epigenetic research.

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“…Modifications to the accessibility of genes, by regulation of these structures, are termed epigenetic regulation and have also been found to be an integral component in the development of addiction. Given that the epigenetic control of drug addiction has been elegantly reviewed in previous work [14][15][16][17], this chapter focuses on other aspects of gene expression control starting at the level of transcription.…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms of Drug-Induced Plasticity

Oliver¹,

Perrone‐Bizzozero²

2017

Synaptic Plasticity

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Substance-use disorders (SUDs) are a significant societal burden. Like many other conditions, SUDs are characterized by chronic relapse after periods without symptoms. Alterations in synaptic plasticity have been documented after acute and addiction-related behavioral exposures to drugs of abuse. These synaptic alterations are persistent and similar to the chronic relapse state of patients with SUDs, suggesting that reversing these synaptic alterations may prevent relapse. Additionally, many of these synaptic features of addiction mirror those found in other forms of learning and memory. These features suggest that the etiology of this disorder stems from persistent modifications in corticolimbic synaptic plasticity mediated by drug-induced alterations in addiction-related gene (ARG) expression. Understanding the regulation of addiction-related genes and their impact on synaptic plasticity and behavior may inform new pharmacological treatments that reverse these aberrant drug-evoked forms of plasticity in favor of remission.

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Epigenetics and addiction

Cited by 27 publications

References 76 publications

Differential Expression of mRNAs Coding for Histone Deacetylases (HDACs) in the Nucleus Accumbens of Compulsive Methamphetamine Takers and Abstinent Rats

Differential Expression of mRNAs Coding for Histone Deacetylases (HDACs) in the Nucleus Accumbens of Compulsive Methamphetamine Takers and Abstinent Rats

Epigenetic Research in Neuropsychiatric Disorders: the “Tissue Issue”

Molecular Mechanisms of Drug-Induced Plasticity

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