Histone-Mediated Epigenetics in Addiction

Hitchcock, Leah N.; Lattal, K. Matthew

doi:10.1016/b978-0-12-800977-2.00003-6

Cited by 19 publications

(13 citation statements)

References 146 publications

(189 reference statements)

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“…Recent finding also suggest that palatable food self-administration during abstinence, as a means of maintaining voluntary abstinence, may also block the development of the incubation of heroin, but not methamphetamine seeking (Venniro et al 2016). The results from these studies have also revealed a number of potential targets for preventing drug relapse such as orexin receptors (Schmeichel et al 2015), brain-derived neurotrophic factor (Koskela et al 2017), dopamine D3 receptors (Sokoloff and Le Foll 2017), metabotropic glutamate receptors (Pomierny-Chamioło et al 2014), and pathways involved in epigenetic regulation and synaptic plasticity (Hitchcock and Lattal 2014; Wolf 2016).…”

Section: Enhanced Drug-seeking/relapse Vulnerabilitymentioning

confidence: 99%

Modeling the development of drug addiction in male and female animals

Lynch

2018

Pharmacology Biochemistry and Behavior

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An increasing emphasis has been placed on the development and use of animal models of addiction that capture defining features of human drug addiction, including escalation/binge drug use, enhanced motivation for the drug, preference for the drug over other reward options, use despite negative consequences, and enhanced drug-seeking/relapse vulnerability. The need to examine behavior in both males and females has also become apparent given evidence demonstrating that the addiction process occurs differently in males and females. This review discusses the procedures that are used to model features of addiction in animals, as well as factors that influence their development. Individual differences are also discussed, with a particular focus on sex differences. While no one procedure consistently produces all characteristics, different models have been developed to focus on certain characteristics. A history of escalating/binge patterns of use appears to be critical for producing other features characteristic of addiction, including an enhanced motivation for the drug, enhanced drug seeking, and use despite negative consequences. These characteristics tend to emerge over abstinence, and appear to increase rather than decrease in magnitude over time. In females, these characteristics develop sooner during abstinence and/or following less drug exposure as compared to males, and for psychostimulant addiction, may require estradiol. Although preference for the drug over other reward options has been demonstrated in non-human primates, it has been more difficult to establish in rats. Future research is needed to define the parameters that optimally induce each of these features of addiction in the majority of animals. Such models are essential for advancing our understanding of human drug addiction and its treatment in men and women.

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Section: Enhanced Drug-seeking/relapse Vulnerabilitymentioning

confidence: 99%

Modeling the development of drug addiction in male and female animals

Lynch

2018

Pharmacology Biochemistry and Behavior

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“…Recent attention has focused on epigenetic mechanisms that modulate interactions between DNA, histones, and other aspects of chromatin structure (Hitchcock and Lattal, 2014). Many studies have now documented enhancements in memory caused by administration of drugs that inhibit histone deacetylases (HDACs), which prevent the removal of acetyl groups from specific amino acid sites of histones(e.g., Dagnas et al 2015; Foley et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Effects of a histone deacetylase 3 inhibitor on extinction and reinstatement of cocaine self-administration in rats

et al. 2018

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Rationale: A challenge in treating substance use disorder is that successful treatment often does not persist, resulting in relapse and continued drug seeking. One approach to persistently weaken drug-seeking behaviors is to pair exposure to drug-associated cues or behaviors with delivery of a compound that may strengthen the inhibition of the association between drug cues and behavior. Objectives: We evaluated whether a selective histone deacetylase 3 (HDAC3) inhibitor could promote extinction and weaken contextual control of operant drug-seeking after intravenous cocaine self-administration. Methods: Male Long Evans rats received a systemic injection of the HDAC3 inhibitor RGFP966 either before or immediately after the first extinction session. Persistence of extinction was tested over subsequent extinction sessions, as well as tests of reinstatement that included cue-induced reinstatement, contextual renewal, and cocaine-primed reinstatement. Additional extinction sessions occurred between each reinstatement test. We also evaluated effects of RGFP966 on performance and motivation during stable fixed ratio operant responding for cocaine and during a progressive ratio of reinforcement. Results: RGFP966 administered before the first extinction session led to significantly less responding during subsequent extinction and reinstatement tests compared to vehicle-injected rats. Follow-up studies found that these effects were not likely due to a performance deficit or a change in motivation to self-administer cocaine, as injections of RGFP966 had no effect on stable responding during a fixed or progressive ratio schedule. In addition, RGFP966 administered just after the first extinction session had no effect during early extinction and reinstatement tests, but weakened long-term responding during later extinction sessions. Conclusions: These results suggest that a systemic injection of a selective HDAC3 inhibitor can enhance extinction and suppress reinstatement after cocaine self-administration. The finding that behavioral and pharmacological manipulations can be combined to decrease drug-seeking provides further potential for treatment by epigenetic modulation.

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“…Broadly, epigenetics refers to changes in chromatin structure that influence gene expression without affecting gene sequence (Kwapis & Wood ; Levenson & Sweatt ). Two primary mechanisms of epigenetic regulation are through direct DNA methylation and histone modification, and these mechanisms allow for the integration and storage of information in species ranging from yeast and plants up to humans (reviewed in Hitchcock & Lattal ; Vanyushin ). Chromatin refers to the complex of DNA and proteins that reside in the nucleus of a cell, and the primary proteins that comprise chromatin are histones.…”

Section: The Need For a Molecular Approach: Epigenetic Mechanisms In mentioning

confidence: 99%

Epigenetics and memory: causes, consequences and treatments for post‐traumatic stress disorder and addiction

Pizzimenti

Lattal

2015

Genes Brain and Behavior

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Understanding the interaction between fear and reward at the circuit and molecular levels has implications for basic scientific approaches to memory and for understanding the etiology of psychiatric disorders. Both stress and exposure to drugs of abuse induce epigenetic changes that result in persistent behavioral changes, some of which may contribute to the formation of a drug addiction or a stress-related psychiatric disorder. Converging evidence suggests that similar behavioral, neurobiological and molecular mechanisms control the extinction of learned fear and drug-seeking responses. This may, in part, account for the fact that individuals with post-traumatic stress disorder have a significantly elevated risk of developing a substance use disorder and have high rates of relapse to drugs of abuse, even after long periods of abstinence. At the behavioral level, a major challenge in treatments is that extinguished behavior is often not persistent, returning with changes in context, the passage of time or exposure to mild stressors. A common goal of treatments is therefore to weaken the ability of stressors to induce relapse. With the discovery of epigenetic mechanisms that create persistent molecular signals, recent work on extinction has focused on how modulating these epigenetic targets can create lasting extinction of fear or drug-seeking behavior. Here, we review recent evidence pointing to common behavioral, systems and epigenetic mechanisms in the regulation of fear and drug seeking. We suggest that targeting these mechanisms in combination with behavioral therapy may promote treatment and weaken stress-induced relapse.

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Histone-Mediated Epigenetics in Addiction

Cited by 19 publications

References 146 publications

Modeling the development of drug addiction in male and female animals

Modeling the development of drug addiction in male and female animals

Effects of a histone deacetylase 3 inhibitor on extinction and reinstatement of cocaine self-administration in rats

Epigenetics and memory: causes, consequences and treatments for post‐traumatic stress disorder and addiction

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