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Behavioral epigenetic, drug abuse.

Candace R Lewis, Ryan Bastle, Tawny B Manning, Sarah M Himes, Paulette Fennig, Phoebe R Conrad, Jenna Colwell, Broc A Pagni, Lyndsay A Hess, Caitlin G Matekel, Jason M Newbern, M Foster Olive
Early life stress (ELS) is highly related to the development of psychiatric illnesses in adulthood, including substance use disorders. A recent body of literature suggests long-lasting changes in the epigenome may be a mechanism by which experiences early in life can alter neurobiological and behavioral phenotypes in adulthood. In this study, we replicate our previous findings that ELS, in the form of prolonged maternal separation, increases adult methamphetamine self-administration (SA) in male rats as compared to handled controls...
June 17, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Michael E Authement, Ludovic D Langlois, Haifa Kassis, Shawn Gouty, Matthieu Dacher, Ryan D Shepard, Brian M Cox, Fereshteh S Nugent
Dopamine (DA) dysfunction originating from the ventral tegmental area (VTA) occurs as a result of synaptic abnormalities following consumption of drugs of abuse and underlies behavioral plasticity associated with drug abuse. Drugs of abuse can cause changes in gene expression through epigenetic mechanisms in the brain that underlie some of the lasting neuroplasticity and behavior associated with addiction. Here we investigated the function of histone acetylation and histone deacetylase (HDAC)2 in the VTA in recovery of morphine-induced synaptic modifications following a single in vivo exposure to morphine...
September 1, 2016: Journal of Neurophysiology
Menahem B Doura, Ellen M Unterwald
Exposure to stress increases vulnerability to drug abuse, as well as relapse liability in addicted individuals. Chronic drug use alters stress response in a manner that increases drug seeking behaviors and relapse. Drug exposure and withdrawal have been shown to alter stress responses, and corticosteroid mediators of stress have been shown to impact addiction-related brain function and drug-seeking behavior. Despite the documented interplay between stress and substance abuse, the mechanisms by which stress exposure and drug seeking interact remain largely unknown...
2016: Frontiers in Cellular Neuroscience
Gretchen E Tietjen, Dawn C Buse, Stuart A Collins
Maltreatment during childhood increases vulnerability to a host of health disorders, including migraine. Putative mechanisms linking maltreatment and migraine include stress-induced dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, as well as disruption of other stress-mediating homeostatic systems, including those involving endocannabinoids, monoamine neurotransmitters, oxytocin, and inflammation. Prolonged elevation of glucocorticoids alters the neural architecture of the limbic system, resulting in the structural as well as functional changes described in both maltreatment and in migraine...
July 2016: Current Treatment Options in Neurology
David Miller, Merlene Miller, Kenneth Blum, Rajendra D Badgaiyan, Marcelo Febo
There are approximately 14,500 clinics and programs in America that provide treatment for all types of addictive behaviors we call "Reward Deficiency Syndrome (RDS)". While most of these have good intentions to provide needed help to the victims of RDS, we propose herein that most of their efforts, especially during periods of aftercare, are not based on the existing scientific evidence. We use "aftercare" to refer to any form of program or therapy following primary treatment including 12-Step programs. Very few programs actually provide any evidenced-based treatment approaches during this most vulnerable period in recovery...
October 21, 2015: Journal of Reward Deficiency Syndrome
Massimo Ubaldi, Nazzareno Cannella, Roberto Ciccocioppo
Drug abuse represents a considerable burden of disease and has enormous economic impacts on societies. Over the years, few medications have been developed for clinical use. Their utilization is endowed with several limitations, including partial efficacy or significant side effects. On the other hand, the successful advancement of these compounds provides an important proof of concept for the feasibility of drug development programs in addiction. In recent years, a wealth of information has been generated on the psychological mechanisms, genetic or epigenetic predisposing factors, and neurobiological adaptations induced by drug consumption that interact with each other to contribute to disease progression...
2016: Progress in Brain Research
Kenneth Blum, Rajendra D Badgaiyan, Mark S Gold
Hypersexuality has been defined as abnormally increased sexual activity. Epidemiological and clinical studies have shown that this non-paraphilic condition consists of "excessive" sexual behaviors and disorders accompanied by personal distress and social and medical morbidity. It is a very controversial and political topic in terms of how best to categorize it as similar or not similar to addictive behaviors including substance abuse. Hypersexual disorder is conceptualized as a non-paraphilic sexual desire disorder with impulsivity...
2015: Curēus
Kenneth Blum, Rajendra D Badgaiyan, Mark S Gold
Hypersexuality is now part of the DSM-V and has been defined as abnormally increased sexual activity. Epidemiological and clinical studies have shown that this non-paraphilic condition consists of "excessive" sexual behaviors and disorders accompanied by personal distress and social and medical morbidity. Hypersexual disorder is conceptualized as primarily a non-paraphilic sexual desire disorder with impulsivity. Pathophysiological perspectives include dysregulation of sexual arousal and desire, sexual impulsivity, sexual addiction, and sexual compulsivity...
July 2015: Curēus
Tuhin Suvro Banerjee, Abhijit Hazra, Nirup Bikash Mondal, Sumantra Das
Opioidergic system plays an important role in controlling alcohol seeking behavior. We have previously shown that a quinoline compound, S4 (2-(2-methylquinolin-4-ylamino)-N-phenyl acetamide), having dual affinity for µ- and κ-opioid receptors, could successfully inhibit withdrawal symptoms in mice rendered dependent on morphine. Accordingly, in the present study, we sought to determine the potential of S4 in attenuating voluntary alcohol intake in alcohol-preferring (AP) mice and the mechanism thereof. The study was conducted in different mice strains initially screened for AP and alcohol-avoiding (AA) behavior...
August 2015: Neurochemistry International
Anti Kalda, Alexander Zharkovsky
Psychostimulant-induced addiction involves potentially life-long behavioral abnormalities that are caused by repeated exposure to a drug of abuse in vulnerable individuals. The persistence of these behavioral changes suggests that long-lasting alterations in gene expression, particularly within the brain's reward regions, may contribute significantly to the addiction phenotype. An increasing number of works over the past decade have demonstrated the important role of epigenetic regulatory events in mediating the lasting effects of drugs of abuse (including psychostimulants, such as cocaine and amphetamine) in animal models of drug addiction...
2015: International Review of Neurobiology
Katherine N Wright, Fiona Hollis, Florian Duclot, Amanda M Dossat, Caroline E Strong, T Chase Francis, Roger Mercer, Jian Feng, David M Dietz, Mary Kay Lobo, Eric J Nestler, Mohamed Kabbaj
Epigenetic mechanisms, such as histone modifications, regulate responsiveness to drugs of abuse, such as cocaine, but relatively little is known about the regulation of addictive-like behaviors by DNA methylation. To investigate the influence of DNA methylation on the locomotor-activating effects of cocaine and on drug-seeking behavior, rats receiving methyl supplementation via chronic l-methionine (MET) underwent either a sensitization regimen of intermittent cocaine injections or intravenous self-administration of cocaine, followed by cue-induced and drug-primed reinstatement...
June 10, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Corey T Watson, Henrietta Szutorisz, Paras Garg, Qammarah Martin, Joseph A Landry, Andrew J Sharp, Yasmin L Hurd
Drug exposure during critical periods of development is known to have lasting effects, increasing one's risk for developing mental health disorders. Emerging evidence has also indicated the possibility for drug exposure to even impact subsequent generations. Our previous work demonstrated that adolescent exposure to Δ(9)-tetrahydrocannabinol (THC), the main psychoactive component of marijuana (Cannabis sativa), in a Long-Evans rat model affects reward-related behavior and gene regulation in the subsequent (F1) generation unexposed to the drug...
December 2015: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Menglu Yuan, Sarah J Cross, Sandra E Loughlin, Frances M Leslie
Adolescence encompasses a sensitive developmental period of enhanced clinical vulnerability to nicotine, tobacco, and e-cigarettes. While there are sociocultural influences, data at preclinical and clinical levels indicate that this adolescent sensitivity has strong neurobiological underpinnings. Although definitions of adolescence vary, the hallmark of this period is a profound reorganization of brain regions necessary for mature cognitive and executive function, working memory, reward processing, emotional regulation, and motivated behavior...
August 15, 2015: Journal of Physiology
Marpadga A Reddy, Rama Natarajan
The growing epidemic of obesity and diabetes, the aging population as well as prevalence of drug abuse has led to significant increases in the rates of the closely associated acute and chronic kidney diseases, including diabetic nephropathy. Furthermore, evidence shows that parental behavior and diet can affect the phenotype of subsequent generations via epigenetic transmission mechanisms. These data suggest a strong influence of the environment on disease susceptibility and that, apart from genetic susceptibility, epigenetic mechanisms need to be evaluated to gain critical new information about kidney diseases...
August 2015: Kidney International
Kenneth Blum, Peter K Thanos, Rajendra D Badgaiyan, Marcelo Febo, Marlene Oscar-Berman, James Fratantonio, Zsolt Demotrovics, Mark S Gold
INTRODUCTION: Addiction is a substantial health issue with limited treatment options approved by the FDA and as such currently available. The advent of neuroimaging techniques that link neurochemical and neurogenetic mechanisms to the reward circuitry brain function provides a framework for potential genomic-based therapies. AREAS COVERED: Through candidate and genome-wide association studies approaches, many gene polymorphisms and clusters have been implicated in drug, food and behavioral dependence linked by the common rubric reward deficiency syndrome (RDS)...
July 2015: Expert Opinion on Biological Therapy
Jean Zwiller
Chronic drug exposure alters gene expression in the brain, which is believed to underlie compulsive drug seeking and drug taking behavior. Recent evidence shows that drug-induced long-term neuroadaptations in the brain are mediated in part by epigenetic mechanisms. By remodeling chromatin, this type of regulation contributes to drug-induced synaptic plasticity that translates into behavioral modifications. How drug-induced alterations in DNA methylation regulate gene expression is reviewed here, with a focus on MeCP2, a protein binding methylated DNA...
April 2015: Médecine Sciences: M/S
Kenneth Blum, Marcelo Febo, David E Smith, A Kenison Roy, Zsolt Demetrovics, Frans J Cronjé, John Femino, Gozde Agan, James L Fratantonio, Subhash C Pandey, Rajendra D Badgaiyan, Mark S Gold
As addiction professionals, we are becoming increasingly concerned about preteenagers and young adults' involvement with substance abuse as a way of relieving stress and anger. The turbulent underdeveloped central nervous system, especially in the prefrontal cortex (PFC), provides impetus to not only continue important neuroimaging studies in both human and animal models, but also to encourage preventive measures and cautions embraced by governmental and social media outlets. It is well known that before people reach their 20s, PFC development is undergoing significant changes and, as such, hijacks appropriate decision making in this population...
May 2015: Journal of Child and Adolescent Psychopharmacology
Hirofumi Morishita, Marija Kundakovic, Lucy Bicks, Amanda Mitchell, Schahram Akbarian
Schizophrenia, a major psychiatric disorder defined by delusions and hallucinations, among other symptoms, often with onset in early adulthood, is potentially associated with molecular and cellular alterations in parvalbumin-expressing fast spiking interneurons and other constituents of the cortical inhibitory GABAergic circuitry. The underlying mechanisms, including the role of disease-associated risk factors operating in adolescence such as drug abuse and social stressors, remain incompletely understood. Here, we summarize emerging findings from animal models, highlighting the ability of parvalbuminergic interneurons (PVI) to induce, during the juvenile period, long-term plastic changes in prefrontal and visual cortex, thereby altering perception, cognition and behavior in the adult...
October 2015: Neurobiology of Learning and Memory
Nicole L Yohn, Marisa S Bartolomei, Julie A Blendy
Familial inheritance of drug abuse is composed of both genetic and environmental factors. Additionally, epigenetic transgenerational inheritance may provide a means by which parental drug use can influence several generations of offspring. Recent evidence suggests that parental drug exposure produces behavioral, biochemical, and neuroanatomical changes in future generations. The focus of this review is to discuss these multigenerational and transgenerational phenotypes in the offspring of animals exposed to drugs of abuse...
July 2015: Progress in Biophysics and Molecular Biology
Ja Wook Koo, Michelle S Mazei-Robison, Quincey LaPlant, Gabor Egervari, Kevin M Braunscheidel, Danielle N Adank, Deveroux Ferguson, Jian Feng, Haosheng Sun, Kimberly N Scobie, Diane M Damez-Werno, Efrain Ribeiro, Catherine Jensen Peña, Deena Walker, Rosemary C Bagot, Michael E Cahill, Sarah Ann R Anderson, Benoit Labonté, Georgia E Hodes, Heidi Browne, Benjamin Chadwick, Alfred J Robison, Vincent F Vialou, Caroline Dias, Zachary Lorsch, Ezekiell Mouzon, Mary Kay Lobo, David M Dietz, Scott J Russo, Rachael L Neve, Yasmin L Hurd, Eric J Nestler
Brain-derived neurotrophic factor (BDNF) has a crucial role in modulating neural and behavioral plasticity to drugs of abuse. We found a persistent downregulation of exon-specific Bdnf expression in the ventral tegmental area (VTA) in response to chronic opiate exposure, which was mediated by specific epigenetic modifications at the corresponding Bdnf gene promoters. Exposure to chronic morphine increased stalling of RNA polymerase II at these Bdnf promoters in VTA and altered permissive and repressive histone modifications and occupancy of their regulatory proteins at the specific promoters...
March 2015: Nature Neuroscience
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