Genome-wide DNA methylation and expression analyses in the nucleus accumbens identifies coordinated regulation of receptor trafficking regulators
DNA methylation modifications have been associated with alcohol use and proposed to contribute to alcohol abuse disorders, however the downstream molecular and cellular consequences remain obscure. We investigated the effects of long-term alcohol use on genome-wide DNA methylation in the nucleus accumbens (NAc) of rhesus macaques that self-administered 4% alcohol for 12 months. Using CpG-rich region enrichment, bisulfite sequencing and cluster analysis to identify differentially methylated regions (DMRs), the methylation levels of 2.7 million CpGs were compared between alcohol-na ïve, light-moderate and heavy drinking sub...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: R. Cervera-Juanes, L.J. Wilhem, K.A. Grant, B. Ferguson Source Type: research
Integrative synaptomics reveals orbitofrontal neuroadaptations and biomarkers in heavy drinking macaques
In this study, we describe maladaptive neuroadaptations in OFC pyramidal neurons in heavy drinking cynomolgus macaques. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Patrick J. Mulholland, Sudarat Nimitvilai, Joachim D. Uys, Kathleen A. Grant, John J. Woodward Source Type: research
Intersection between alcohol use and emotion regulation in adolescents undergoing a stressful life event
One of the most serious stressors that can befall youth in the United States (U.S.) is arrest in the juvenile justice system. In fact, U.S. juvenile justice system involvement is linked to higher levels of alcohol use during adolescence, and sustained trajectories of alcohol-related health impact into adulthood. One reason may be due to disruption of the emotion regulation systems during this neurodevelopmental period. We therefore examined correlates of emotion regulation and alcohol use during this neuro-developmental stage, and within sample of youth experiencing an inherently stressful period (juvenile justice involvem...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: S.W. Feldstein Ewing, K.A. Hudson, A.D. Bryan, B.J. Nagel, D. Fair, J.D. Caouette Source Type: research
Anxiety, depression, and stress in a high-risk college environment: Improving heart rate variability and neurocardiac signaling to prevent relapse
Chronic stress increases cortisol and corticosteroid levels, and reduces heart rate variability (HRV), compromising immune function and heightening anxiety and depression. Reduced HRV decreases people ’s ability to appropriately modulate affective reactivity to the environment, contributing to chronic stress; alcohol and drug misuse further reduces HRV. Effective relapse prevention following addiction treatment needs to interrupt this cycle, yet often is limited to the psychosocial aspects of a ffect and stress management. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: David Eddie, Nour Alayan, Fiona Conway, Marsha Bates Source Type: research
Exploring the intersection of race, stress, and alcohol use among individuals in treatment
A substantive literature links stress and anxiety to poor health outcomes including drinking behavior, among adults seeking treatment for substance use disorders. However, measures of ongoing stress and anxiety are often unrelated to alcohol-use variables. Recently, we identified race as a modulator of use patterns among treatment-seekers. Here, we extend that work to examine the relationships between stress/anxiety and use variables by race among individuals seeking treatment for an alcohol use disorder. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: B. Lewis, J.L. Price, B. Adinoff, S.J. Nixon Source Type: research
Self-assessed stress-level among elderly seeking treatment for alcohol use disorder. A descriptive study
Empirical data regarding the stress-alcohol link in older people (+60 years of age) is largely lacking. In Denmark, as in most other Western Societies, older age groups report drinking to a higher extent than previous cohorts and consequently, an increasing numbers of older people seek treatment for alcohol use disorder. This new patient group represents a treatment challenge because so little is known about the real-world stressors and symptoms that this patient group experiences. As a part of an ongoing international multisite randomized controlled trial testing treatments targeting senior drinkers [the Elderly Study (An...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Anette S øgaard Nielsen, Randi Bilberg, Kjeld Andersen Source Type: research
Stress and the “dark side” in three different genetic epidemiological cohorts
Recently there has been interest in the emergence of a subclinical syndrome of mood disturbance associated with the evolution of the clinical course of alcohol use disorders (AUDs) that has been labeled by Koob and colleagues the “dark side” of addiction. The present study sought to operationalize a “dark side” phenotype using items from a standard assessment instrument (the semi structured assessment for the genetics of alcoholism (SSAGA)), estimate its prevalence in individuals with AUDs, determine its co-morbidity with other psychiatric disorders, and test its heritability and association with genetic sequence v...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Cindy L. Ehlers, David A. Gilder, Ian Gizer, Qian Peng, Chris Bizon, Kirk Wilhelmsen Source Type: research
Amgydalocortical connectivity at rest is associated with increased reactivity to social threat, ACTH, and future ethanol self-administration
Aggression and anxiety are linked to heavier alcohol use and these phenotypes are associated with dysregulated corticolimbic circuitry and HPA function. Prior to ethanol self-administration, male and female rhesus macaques underwent the Human Intruder Test to assess aggressive and anxious behavior and MRI imaging to assess resting state functional connectivity (rsFC) between the amygdala and prefrontal cortex. Basal cortisol and ACTH were also assayed. After induction of ethanol self-administration with a schedule-induced polydipsia procedure, 4% w/v ethanol access was available for 22 hours/day. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Megan N. McClintick, Damien Fair, Christopher Kroenke, Kathleen A. Grant Source Type: research
Prevention of underage drinking and alcohol use disorders in native American adolescents: Influence of stress and dark side symptoms
This study evaluated 300 American Indian adolescents, ages 13 –17, for factors associated with age of first drink (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: D. Gilder, R. Moore, J. Geisler, D. Calac, J. Luna, C. Ehlers Source Type: research
Physical pain in alcohol-dependent patients entering treatment – Prevalence and risk of post-treatment relapse
Background: Chronic pain and harmful alcohol use commonly co-exist, however, it is not clear how presence of pain may impact risk of relapse in alcoholism. The purpose of the study was to characterize pain in a group of alcohol-dependent individuals entering treatment programs and to examine if changes in pain before and after the treatment influences risk of post-treatment relapse. Methods: A sample of 366 alcohol-dependent subjects was recruited in alcohol treatment centers in Warsaw, Poland. Information was obtained about demographics, social functioning, childhood abuse, severity of alcohol and sleep problems, level of...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Marcin Wojnar, Andrzej Jakubczyk, Maciej Kopera, Anna Klimkiewicz, Aleksandra Krasowska, Mark A. Ilgen, Frederic C. Blow, Amy Bohnert, Kirk J. Brower Source Type: research
Convergence of central pain and stress signaling in alcohol dependence
A key feature of severe alcohol use disorder (AUD) is the emergence of negative affective states that can influence the motivational properties of alcohol. Pain represents one such negative emotional state hypothesized to drive AUD severity, and this relationship is particularly concerning since there are few effective treatments for either chronic pain or AUD. Ascending nociceptive circuitry alters the function of central brain stress and reinforcement systems, and excessive alcohol exposure also produces neuroadaptations within nociceptive-terminal brain regions, including the central amygdala and cingulate cortex. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Scott Edwards Source Type: research
Social transfer of alcohol withdrawal induced hyperalgesia
Chronic pain often manifests in the absence of tissue damage, and is greatly impacted by social and environmental factors. Because chronic pain and alcohol dependence are interrelated, we examined pain during withdrawal from voluntary alcohol drinking in male C57BL/6J mice. Our findings reveal hyperalgesia not only in “primary” alcohol-withdrawn mice, but also in water-drinking “bystander” control mice housed in the same room. This phenomenon generalizes to other pain states, as evidenced by the social transfer of morphine withdrawal-induced and inflammatory hyperalgesia. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Monique L. Smith, Andre Walcott, Caroline Hostetler, Andrey E. Ryabinin, Mary M. Heinricher Source Type: research
Altered voluntary alcohol intake after induction and relief of chronic pain symptoms in rats
Purpose: Chronic pain states affect alcohol use patterns and promote the development of alcoholism, while long-term alcohol dependence induces symptoms of hyperalgesia and may exacerbate chronic pain arising from other sources. To study the complex relationship between chronic pain and alcohol dependence we sought to develop rodent models that combine chronic pain with alcohol dependence. Methods: Model 1: we induced unilateral neuropathy symptoms of mechanical allodynia by sciatic nerve entrapment (SNE) in male Sprague Dawley rats. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Igor Spigelman, Yatendra Mulpuri, David H. Terry, Marijo L. Pempe ña, Kha Nguyen, Vincent N. Marty Source Type: research
Epigenetic enzymes as a novel class of targets for disease-modifying pharmacotherapies in alcohol addiction
Alcohol dependence leads to escalation of alcohol intake, increased aversion-resistant alcohol taking ( “compulsivity”), and increased sensitivity to stress-induced relapse. We have shown that the emergence of these traits is in part driven by a coordinated and persistent dysregulations of gene expression networks in the medial prefrontal cortex (mPFC). Recently, we identified several novel candid ates that might be mechanistically related to alcohol-addiction relevant phenotypes, and offer targets for disease-modifying pharmacotherapies. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: E. Barbier, A.L. Johnstone, B.B. Khomtchouk, J.D. Tapocik, C. Pitcairn, F. Rehman, E. Augier, A. Borich, J.R. Schank, C.A. Rienas, D.J. Van Booven, H. Sun, D. N ätt, C. Wahlestedt, M. Heilig Source Type: research
Involvement of α4β2 and α3β4 nicotinic receptor subtypes in alcohol taking and seeking
Preclinical and clinical evidence has indicated that nicotinic acetylcholine receptors (nAChRs) are important pharmacological targets for treatment of alcoholism. However, it is unclear which specific nAChR subtypes serve as mediators of the rewarding effects of alcohol due, in part, to the lack of potent and selective ligands for the different possible combinations of the subunits that compose nAChRs. Using combinatorial mixture libraries, Assuage Pharmaceuticals, in collaboration with Torrey Pines Institute for Molecular Studies has discovered high affinity nAChR antagonists with exquisite selectivity for α4β2 nAChRs o...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Andrea Cippitelli, Jinhua Wu, Ginamarie Debevec, Christopher Armishaw, Greg S. Welmaker, Marc Giulianotti, Lawrence Toll Source Type: research
