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Protracted Withdrawal

Brittany A Matthews, Junchao Tong, Sophia Attwells, Xin Xu, Anh Le, Stephen J Kish, Jeffrey H Meyer
BACKGROUND: A key component of alcohol dependence (AD), a severe form of alcohol use disorder, is the negative emotional state during withdrawal. Monoamine oxidase A (MAO-A) is an important enzyme that metabolizes monoamines and creates oxidative stress. Elevations in MAO-A level, especially in the prefrontal and anterior cingulate cortex (PFC and ACC), are associated with low mood states, including the dysphoria of early alcohol withdrawal in humans. The aim of the present study was to determine whether chronic alcohol vapor exposure causes an upregulation of MAO-A activity or level in the PFC and ACC of rodents during acute withdrawal...
February 5, 2018: Drug and Alcohol Dependence
Albert J Czaja
Autoimmune hepatitis lacks a quantifiable biomarker that is close to its pathogenic mechanisms and that accurately reflects inflammatory activity, correlates with treatment response, and ensures inactive disease before treatment withdrawal. Areas covered: Micro-ribonucleic acids, programmed death-1 protein and its ligands, macrophage migration inhibitory factor, soluble CD163, B cell activating factor, and metabolite patterns in blood were considered the leading candidates as therapeutic biomarkers after search of PubMed from August 1981 to August 2017 using the search words "biomarkers of autoimmune hepatitis"...
March 14, 2018: Expert Review of Gastroenterology & Hepatology
Rimenez R Souza, Nicole M Robertson, David T Pruitt, Lindsey Noble, Eric C Meyers, Phillip A Gonzales, Nathaniel P Bleker, Holle L Carey, Seth A Hays, Michael P Kilgard, Christa K McIntyre, Robert L Rennaker
BACKGROUND: Fear conditioning (FC) in rodents is the most used animal model to investigate the neurobiology of posttraumatic stress disorder (PTSD). Although research using FC has generated a better understanding of fear memories, studies often rely on mild or moderate FC training and behavioral analysis generally focuses on measuring freezing responses within few test sessions. NEW METHOD: We introduce the M-Maze task, a system to measures extinction of conditioned fear using suppression of operant behavior...
February 13, 2018: Journal of Neuroscience Methods
Igor Bazov, Daniil Sarkisyan, Olga Kononenko, Hiroyuki Watanabe, Tatiana Yakovleva, Anita C Hansson, Wolfgang H Sommer, Rainer Spanagel, Georgy Bakalkin
Molecular changes induced by excessive alcohol consumption may underlie formation of dysphoric state during acute and protracted alcohol withdrawal which leads to craving and relapse. A main molecular addiction hypothesis is that the upregulation of the dynorphin (DYN)/κ-opioid receptor (KOR) system in the nucleus accumbens (NAc) of alcohol-dependent individuals causes the imbalance in activity of D1- and D2 dopamine receptor (DR) expressing neural circuits that results in dysphoria. We here analyzed post-mortem NAc samples of human alcoholics to assess changes in prodynorphin (PDYN) and KOR (OPRK1) gene expression and co-expression (transcriptionally coordinated) patterns...
January 30, 2018: Molecular Neurobiology
Elizabeth A Osterndorff-Kahanek, Gayatri R Tiwari, Marcelo F Lopez, Howard C Becker, R Adron Harris, R Dayne Mayfield
Long-term alcohol use can result in lasting changes in brain function, ultimately leading to alcohol dependence. These functional alterations arise from dysregulation of complex gene networks, and growing evidence implicates microRNAs as key regulators of these networks. We examined time- and brain region-dependent changes in microRNA expression after chronic intermittent ethanol (CIE) exposure in C57BL/6J mice. Animals were sacrificed at 0, 8, and 120h following the last exposure to four weekly cycles of CIE vapor and we measured microRNA expression in prefrontal cortex (PFC), nucleus accumbens (NAC), and amygdala (AMY)...
2018: PloS One
Manuel Sanchez-Alavez, Derek N Wills, Leslie Amodeo, Cindy L Ehlers
BACKGROUND: Disturbances in sleep architecture, especially reductions in slow-wave sleep (SWS), are symptoms commonly observed in individuals with alcohol use disorders. Recent clinical trials have demonstrated that the anticonvulsant and analgesic drug gabapentin may have therapeutic value in normalizing sleep quality in recovering alcoholics. However, the brain mechanisms underlying this improvement in sleep following gabapentin treatment remain unknown. METHODS: In this study, adult Wistar rats were exposed to 8 weeks of chronic intermittent ethanol [EtOH] vapor (blood EtOH concentrations averaged 128...
March 2018: Alcoholism, Clinical and Experimental Research
Mohammed Akbar, Mark Egli, Young-Eun Cho, Byoung-Joon Song, Antonio Noronha
Patients who suffer from alcohol use disorders (AUDs) usually go through various socio-behavioral and pathophysiological changes that take place in the brain and other organs. Recently, consumption of unhealthy food and excess alcohol along with a sedentary lifestyle has become a norm in both developed and developing countries. Despite the beneficial effects of moderate alcohol consumption, chronic and/or excessive alcohol intake is reported to negatively affect the brain, liver and other organs, resulting in cell death, organ damage/failure and death...
December 2, 2017: Pharmacology & Therapeutics
L G Kolik, A V Nadorova, S B Seredenin
Activity of hemantane, an amino adamantane derivative, exhibiting the properties of lowaffinity non-competitive NMDA receptor antagonist, was evaluated in experimental in vivo models of alcoholism. Hemantane had no effects on the formation and manifestation of behavioral sensitization to ethanol in DBA/2 mice. Under conditions of free choice between 10% ethanol and water, hemantane (20 mg/kg/day for 14 days, intraperitoneally) significantly reduced the daily ethanol intake in random-bred male rats with formed alcohol motivation (>4 g/kg of ethanol)...
December 2017: Bulletin of Experimental Biology and Medicine
Karen K Szumlinski, Christina B Shin
A diagnostic criterion for drug addiction, persistent drug-craving continues to be the most treatment-resistant aspect of addiction that maintains the chronic, relapsing, nature of this disease. Despite the high prevalence of psychomotor stimulant addiction, there currently exists no FDA-approved medication for craving reduction. In good part, this reflects our lack of understanding of the neurobiological underpinnings of drug-craving. In humans, cue-elicited drug-craving is associated with the hyper-excitability of prefrontal cortical regions...
November 20, 2017: Genes, Brain, and Behavior
K M Lee, M A Coelho, K R Sern, K K Szumlinski
A history of binge-drinking decreases protein expression of the glutamate-related scaffolding protein Homer2 within the central nucleus of the amygdala (CEA), coinciding with behavioral signs of negative affect. To assess the functional relevance of this protein change for withdrawal-induced hyper-anxiety, adult (PND 56) and adolescent (PND 28) male C57BL/6J mice were administered an intra-CEA infusion of an adeno-associated viral vector (AAV) carrying either cDNA to express Homer2 (H2-cDNA) or GFP as control...
January 2018: Neuropharmacology
Uayporn Kaosombatwattana, Julajak Limsrivilai, Ananya Pongpaibul, Monthira Maneerattanaporn, Phunchai Charatcharoenwitthaya
RATIONALE: Mefenamic acid-induced enteropathy may be an under-recognized condition because few reported cases and no review of literature to comprehensively describe all reported cases exist. From inception until February 2017, a systematic literature search identified twenty original reports of cases of mefenamic acid-induced enteropathy. Additional five cases were identified at our hospital. All cases were included in the analyses. PATIENT CONCERNS: Most patients had been regularly taking therapeutic dosages of mefenamic acid for at least three months before symptoms developed...
November 2017: Medicine (Baltimore)
Christina B Shin, Taylor J Templeton, Alvin S Chiu, Jennifer Kim, Ellen S Gable, Philip A Vieira, Tod E Kippin, Karen K Szumlinski
The incubation of cue-reinforced cocaine-seeking coincides with increased extracellular glutamate within the ventromedial prefrontal cortex (vmPFC). The vmPFC is comprised of two subregions that oppositely regulate drug-seeking, with infralimbic (IL) activity inhibiting, and prelimibic (PL) activity facilitating, drug-seeking. Thus, we hypothesized that increasing and decreasing endogenous glutamate within the IL would attenuate and potentiate, respectively, cue-reinforced drug-seeking behavior, with the converse effects observed upon manipulations of endogenous glutamate within the PL...
January 2018: Neuropharmacology
Walter Francesconi, Attila Szücs, Fulvia Berton, George F Koob, Leandro F Vendruscolo, Pietro Paolo Sanna
RATIONALE: Drugs of abuse can alter circuit dynamics by modifying synaptic efficacy and/or the intrinsic membrane properties of neurons. The juxtacapsular subdivision of the bed nucleus of stria terminalis (jcBNST) has unique connectivity that positions it to integrate cortical and amygdala inputs and provide feed-forward inhibition to the central nucleus of the amygdala (CeA), among other regions. In this study, we investigated changes in the synaptic and intrinsic properties of neurons in the rat jcBNST during protracted withdrawal from morphine dependence using a combination of conventional electrophysiological methods and the dynamic clamp technique...
December 2017: Psychopharmacology
Julia Morud, Joakim Strandberg, Anna Andrén, Mia Ericson, Bo Söderpalm, Louise Adermark
Due to the highly addictive properties of nicotine, a low percentage of users successfully maintain cessation for longer periods of time. This might be linked to neuroadaptations elicited by the drug, and understanding progressive changes in neuronal function might provide critical insight into nicotine addiction. We have previously shown that neurotransmission in the nucleus accumbens (nAc), a key brain region with respect to drug reinforcement and relapse, is suppressed for as long as seven months after a brief period of nicotine treatment...
January 2018: Neuropharmacology
Ronald Kim, Marian T Sepulveda-Orengo, Kati L Healey, Emily A Williams, Kathryn J Reissner
Downregulation of the astroglial glutamate transporter GLT-1 is observed in the nucleus accumbens (NAc) following administration of multiple drugs of abuse. The decrease in GLT-1 protein expression following cocaine self-administration is dependent on both the amount of cocaine self-administered and the length of withdrawal, with longer access to cocaine and longer withdrawal periods leading to greater decreases in GLT-1 protein. However, the mechanism(s) by which cocaine downregulates GLT-1 protein remains unknown...
January 2018: Neuropharmacology
Alison M Fixsen, Damien Ridge
Benzodiazepines are a group of drugs used mainly as sedatives, hypnotics, antiepileptics, and muscle relaxants. Consumption is recommended for 2 to 4 weeks only, due to fast onset of dependency and potentially distressing withdrawal symptoms. Few peer-review studies have drawn on the user experiences and language to appreciate firsthand experiences of benzodiazepine withdrawal or discontinuation syndrome. We looked extensively at patient stories of benzodiazepine withdrawal and recovery on Internet support sites and YouTube...
September 1, 2017: Qualitative Health Research
Adam Kimbrough, Giordano de Guglielmo, Jenni Kononoff, Marsida Kallupi, Eric P Zorrilla, Olivier George
BACKGROUND: In humans, emotional and physical signs of withdrawal from ethanol are commonly seen. Many of these symptoms, including anxiety-like and depression-like behavior, have been characterized in animal models of ethanol dependence. One issue with several current behavioral tests that measure withdrawal in animal models is that they are often not repeatable within subjects over time. Additionally, irritability, one of the most common symptoms of ethanol withdrawal in humans, has not been well characterized in animal models...
November 2017: Alcoholism, Clinical and Experimental Research
Mei-Fang Gong, Rui-Ting Wen, Ying Xu, Jian-Chun Pan, Ning Fei, Yan-Meng Zhou, Jiang-Ping Xu, Jian-Hui Liang, Han-Ting Zhang
RATIONALE: Withdrawal symptoms stand as a core feature of alcohol dependence. Our previous results have shown that inhibition of phosphodiesterase-4 (PDE4) decreased ethanol seeking and drinking in alcohol-preferring rodents. However, little is known about whether PDE4 is involved in ethanol abstinence-related behavior. OBJECTIVE: The objective of this study was to characterize the role of PDE4 in the development of anxiety- and depressive-like behavior induced by abstinence from ethanol exposure in different animal models...
October 2017: Psychopharmacology
Kaziya M Lee, Michal A Coehlo, Noah R Solton, Karen K Szumlinski
Binge-drinking is common in underage alcohol users, yet we know little regarding the biopsychological impact of binge-drinking during early periods of development. Prior work indicated that adolescent male C57BL6/J mice with a 2-week history of binge-drinking (PND28-41) are resilient to the anxiogenic effects of early alcohol withdrawal. Herein, we employed a comparable Drinking-in-the-Dark model to determine how a prior history of binge-drinking during adolescence (EtOH(adolescents)) influences emotionality (assayed with the light-dark box, marble burying test, and the forced swim test) and the propensity to consume alcohol in later life, compared to animals without prior drinking experience...
2017: Frontiers in Psychology
James Davies, Todd C Rae, Luke Montagu
BACKGROUND: Current British National Formulary (BNF) guidelines state that benzodiazepines and zolpidem, zopiclone, and zaleplon, commonly known as Z-drugs (BZD), be prescribed for no more than 4 weeks, although anecdotal data suggest that many patients are prescribed BZDs for much longer. As there are no recent, evidence-based estimates of long-term (>12 months) BZD use in the UK, the scale of this potential problem is unknown. AIM: To produce the first reliable, evidence-based estimate of long-term BZD use in the UK...
September 2017: British Journal of General Practice: the Journal of the Royal College of General Practitioners
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