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Addiction Biology

Anne Koopmann, Patrick Bach, Rilana Schuster, Jan Malte Bumb, Sabine Vollstädt-Klein, Iris Reinhard, Marcella Rietschel, Stephanie H Witt, Klaus Wiedemann, Falk Kiefer
Ghrelin has been shown to be involved in the pathophysiology of alcohol dependence, affecting alcohol self-administration and craving. However, the mechanism of action in alcohol dependence still has to be determined. We thus investigated whether ghrelin is associated with mesolimbic cue reactivity to alcohol cues and alcohol craving in recently detoxified alcohol-addicted subjects. We included 41 recently detoxified alcohol-dependent individuals. Functional magnetic resonance imaging (fMRI) was used to study mesolimbic cue reactivity during the presentation of alcohol-related pictures...
July 9, 2018: Addiction Biology
Shannyn G Genders, Karlene J Scheller, Emily J Jaehne, Bradley J Turner, Andrew J Lawrence, Susanne M Brunner, Barbara Kofler, Maarten van den Buuse, Elvan Djouma
Galanin is a neuropeptide which mediates its effects via three G-protein coupled receptors (GAL1-3 ). Administration of a GAL3 antagonist reduces alcohol self-administration in animal models while allelic variation in the GAL3 gene has been associated with an increased risk of alcohol use disorders in diverse human populations. Based on the association of GAL3 with alcoholism, we sought to characterize drug-seeking behavior in GAL3 -deficient mice for the first time. In the two-bottle free choice paradigm, GAL3 -KO mice consistently showed a significantly increased preference for ethanol over water when compared to wildtype littermates...
July 9, 2018: Addiction Biology
Maria A De Luca, Matthew W Buczynski, Gaetano Di Chiara
Loren (Larry) H. Parsons passed away at the age of 51. In spite of his premature departure, Larry much contributed to the drug abuse field. Since his graduate studies for the Ph.D. in Chemistry in J.B. Justice lab, microdialysis is the tread that links Larry's research topics, namely, the role of dopamine (DA), serotonin (5-HT), gamma-aminobutyric acid (GABA), glutamate and endocannabinoids (eCBs) in drug reinforcement and dependence. Larry was the first to show that abstinence from chronic cocaine reduces extracellular DA in the NAc, consistent with the so called 'dopamine depletion hypothesis' of cocaine addiction...
June 27, 2018: Addiction Biology
Reagan R Wetherill, Hengyi Rao, Nathan Hager, Jieqiong Wang, Teresa R Franklin, Yong Fan
Cigarette smoking continues to be a leading cause of preventable morbidity and mortality. Although the majority of smokers report making a quit attempt in the past year, smoking cessation rates remain modest. Thus, developing accurate, data-driven methods that can classify and characterize the neural features of nicotine use disorder (NUD) would be a powerful clinical tool that could aid in optimizing treatment development and guide treatment modifications. This investigation applied support vector machine-based classification to resting-state functional connectivity (rsFC) data from individuals diagnosed with NUD (n = 108; 63 male) and matched nonsmoking controls (n = 108; 63 male) and multi-dimensional scaling to visualize the heterogeneity of NUD in individual smokers based on rsFC measures...
June 27, 2018: Addiction Biology
Amir Ghaderi, Hamid Reza Banafshe, Naghmeh Mirhosseini, Maryam Motmaen, Fatemeh Mehrzad, Fereshteh Bahmani, Esmat Aghadavod, Mohammad Ali Mansournia, Russel J Reiter, Mohammad-Amin Karimi, Zatollah Asemi
This investigation was designed to determine the effect of melatonin supplementation on mental health parameters, metabolic and genetic profiles in patients under methadone maintenance treatment (MMT). This randomized, double-blind, placebo-controlled, clinical trial was conducted among 54 patients under MMT. Participants were randomly allocated to receive either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 26) or placebo (n = 28) once a day, 1 hour before bedtime for 12 weeks. Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (β -4...
June 27, 2018: Addiction Biology
Scott E Hemby, Scot McIntosh, Francisco Leon, Stephen J Cutler, Christopher R McCurdy
Kratom, derived from the plant Mitragyna speciosa, is receiving increased attention as an alternative to traditional opiates and as a replacement therapy for opiate dependence. Mitragynine (MG) and 7-hydroxymitragynine (7-HMG) are major psychoactive constituents of kratom. While MG and 7-HMG share behavioral and analgesic properties with morphine, their reinforcing effects have not been examined to date. 7-HMG, but not MG, substituted for morphine self-administration in a dose-dependent manner in the rat self-administration paradigm...
June 27, 2018: Addiction Biology
Florence Allain, Anne-Noël Samaha
In rats, continuous cocaine access during long self-administration sessions (6 versus 1-2 hours) promotes the development of behavioral symptoms of addiction. This has led to the assumption that taking large amounts of drug during extended daily bouts is necessary to develop an addiction phenotype. Recent work shows that within-session intermittent access (IntA) to cocaine produces much less drug intake than continuous-access procedures (i.e. long-access sessions) but evokes addiction symptoms more effectively...
June 19, 2018: Addiction Biology
Nathan M Holmes, Jiajing Pan, Andrew Davis, Marios C Panayi, Kelly J Clemens
Restricting when and where smoking can occur is a major focus of public health policies in Western countries. In conjunction with increased taxation, these approaches have contributed to a reduction in smoking uptake among adolescents, yet the consequences for established smokers are less clear. In order to further explore this relationship, we developed a novel animal model of restricted nicotine self-administration. Rats were trained to choose between three doses of nicotine (15, 30 and 60 μg/kg/infusion) under conditions where nicotine was (1) freely available at a low cost (20-second post-infusion time-out, fixed-ratio 1 [FR1]), (2) available under restricted access at a low cost (300-second post-infusion time-out, FR1), or (3) freely available at a high cost (20-second post-infusion time-out, FR5)...
June 19, 2018: Addiction Biology
Ana-Clara Bobadilla, Constanza Garcia-Keller, Victoria Chareunsouk, Jeffrey Hyde, Daniela Medina Camacho, Jasper A Heinsbroek, Peter W Kalivas
Brain-derived neurotrophic factor (BDNF) regulates a variety of physiological processes, and several studies have explored the role of BDNF in addiction-related brain regions like the nucleus accumbens core (NAcore). We sought to understand the rapid effects of endogenous BDNF on cocaine seeking. Rats were trained to self-administer cocaine and extinguished. We then microinjected two inhibitors of BDNF stimulation of tropomyosin receptor kinase B (TrkB), the non-competitive receptor antagonist ANA-12 and TrkB/Fc, a fusion protein that binds BDNF and prevents TrkB stimulation...
June 11, 2018: Addiction Biology
Jérôme Jeanblanc, Pierre Sauton, Virginie Jeanblanc, Rémi Legastelois, Victor Echeverry-Alzate, Sophie Lebourgeois, Maria Del Carmen Gonzalez-Marin, Mickaël Naassila
Binge drinking (BD) is often defined as a large amount of alcohol consumed in a 'short' period of time or 'per occasion'. In clinical research, few researchers have included the notion of 'speed of drinking' in the definition of BD. Here, we aimed to describe a novel pre-clinical model based on voluntary operant BD, which included both the quantity of alcohol and the rapidity of consumption. In adult Long-Evans male rats, we induced BD by regularly decreasing the duration of ethanol self-administration from 1-hour to 15-minute sessions...
June 4, 2018: Addiction Biology
Sambu Seo, Anne Beck, Caroline Matthis, Alexander Genauck, Tobias Banaschewski, Arun L W Bokde, Uli Bromberg, Christian Büchel, Erin Burke Quinlan, Herta Flor, Vincent Frouin, Hugh Garavan, Penny Gowland, Bernd Ittermann, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Luise Poustka, Sarah Hohmann, Juliane H Fröhner, Michael N Smolka, Henrik Walter, Robert Whelan, Sylvane Desrivières, Andreas Heinz, Gunter Schumann, Klaus Obermayer
Abnormalities across different domains of neuropsychological functioning may constitute a risk factor for heavy drinking during adolescence and for developing alcohol use disorders later in life. However, the exact nature of such multi-domain risk profiles is unclear, and it is further unclear whether these risk profiles differ between genders. We combined longitudinal and cross-sectional analyses on the large IMAGEN sample (N ≈ 1000) to predict heavy drinking at age 19 from gray matter volume as well as from psychosocial data at age 14 and 19-for males and females separately...
May 30, 2018: Addiction Biology
Bart de Laat, Akila Weerasekera, Gil Leurquin-Sterk, Willy Gsell, Guy Bormans, Uwe Himmelreich, Cindy Casteels, Koen Van Laere
In a longitudinal rat model of alcohol consumption, we showed that exposure to alcohol decreased the concentration of glutamate in the prefrontal cortex, whereas a normalization occurred during abstinence. 18F-FPEB PET scans revealed that pre-exposure mGluR5 availability in the nucleus accumbens was associated with future alcohol preference. Finally, alcohol exposure induced a decrease in mGluR5 availability in the bilateral hippocampus and amygdala compared with baseline, and in the hippocampus and striatum compared with saccharin (Figure)...
May 23, 2018: Addiction Biology
Andrea B Schote, Kristina Jäger, Sara L Kroll, Matthias Vonmoos, Lea M Hulka, Katrin H Preller, Jobst Meyer, Edna Grünblatt, Boris B Quednow
Animal and cross-sectional human studies suggest that chronic cocaine use is associated with altered responsivity of the hypothalamic-pituitary-adrenal axis to stress. Moreover, increased susceptibility to stress has been proposed as an important factor for development, maintenance and relapse of cocaine addiction. As the glucocorticoid receptor gene (NR3C1) mediates genomic effects of the stress hormone cortisol, we investigated NR3C1 expression and the association of NR3C1 genotypes with cocaine use, addiction and comorbid psychiatric symptoms in 126 chronic cocaine users and 98 stimulant-naïve healthy controls...
May 15, 2018: Addiction Biology
Kassi L Kosnicki, Jerrold C Penprase, Patricia Cintora, Pedro J Torres, Greg L Harris, Susan M Brasser, Scott T Kelley
Many alcohol-induced health complications are directly attributable to the toxicity of alcohol or its metabolites, but another potential health impact of alcohol may be on the microbial communities of the human gut. Clear distinctions between healthy and diseased-state gut microbiota have been observed in subjects with metabolic diseases, and recent studies suggest that chronic alcoholism is linked to gut microbiome dysbiosis. Here, we investigated the effects of moderate levels of alcohol consumption on the gut microbiome in both rats and humans...
May 11, 2018: Addiction Biology
Mojdeh Fattahi, Ghorbangol Ashabi, Seyed Morteza Karimian, Esmail Riahi
Deep brain stimulation (DBS) has been proposed as a promising intervention for patients with treatment-refractory substance use disorder. Here, we investigated if high-frequency DBS in the lateral hypothalamic area (LHA) could affect drug-induced reinforcement. Rats were bilaterally implanted with bipolar stimulation electrodes in the LHA and trained to the morphine conditioned place preference. DBS (monophasic square pulses, 130 Hz, 100-microsecond pulse duration and 150 μA) was applied during the morphine-pairing trials (30 minutes daily for 4 days) or drug-free postconditioning test (15 minutes) to determine its effect on the acquisition or expression of morphine reward, respectively...
May 8, 2018: Addiction Biology
Richard J Macatee, Sarah A Okey, Brian J Albanese, Norman B Schmidt, Jesse R Cougle
Prevalence of cannabis use is increasing, but many regular users do not develop cannabis use disorder (CUD); thus, CUD risk identification among current users is vital for targeted intervention development. Existing data suggest that high distress intolerance (DI), an individual difference reflective of the ability to tolerate negative affect, may be linked to CUD, but no studies have tested possible neurophysiological mechanisms. Increased motivated attentional processing of cannabis and negative emotional stimuli as indexed by neurophysiology [i...
May 7, 2018: Addiction Biology
Seven E Tomek, Gabriela M Stegmann, M Foster Olive
Opioid use disorders are characterized in part by impairments in social functioning. Previous research indicates that laboratory rats, which are frequently used as animal models of addiction-related behaviors, are capable of prosocial behavior. For example, under normal conditions, when a 'free' rat is placed in the vicinity of rat trapped in a plastic restrainer, the rat will release or 'rescue' the other rat from confinement. The present study was conducted to determine the effects of heroin on prosocial behavior in rats...
May 4, 2018: Addiction Biology
Segev Barak, Somayeh Ahmadiantehrani, Marian L Logrip, Dorit Ron
Glial cell line-derived neurotrophic factor (GDNF) has been extensively studied for its role in the development and maintenance of the midbrain dopaminergic system, although evidence suggests that GDNF also plays a role in drug and alcohol addiction. This review focuses on the unique actions of GDNF in the mechanisms that prevent the transition from recreational alcohol use to abuse. Specifically, we describe studies in rodents suggesting that alcohol acutely increases GDNF expression in the ventral tegmental area, which enables the activation of the mitogen-activated protein kinase signaling pathway and the gating of alcohol intake...
May 4, 2018: Addiction Biology
Rachel M Haake, Elizabeth A West, Xuefei Wang, Regina M Carelli
Negative reinforcement models postulate that addicts use drugs to alleviate negative affective states (e.g. dysphoria) associated with withdrawal. In a pre-clinical model, rats exhibit negative affect to a normally rewarding tastant when it predicts impending, but delayed cocaine, and nucleus accumbens (NAc) neurons dynamically track this state. Here, we examined the effects of short versus prolonged experimenter-imposed cocaine abstinence on negative affect, cocaine seeking and self-administration. Rats were given 14 saccharin-cocaine sessions; NAc activity and affective responses to the taste (i...
May 2, 2018: Addiction Biology
Gil Leurquin-Sterk, Jenny Ceccarini, Cleo Lina Crunelle, Akila Weerasekera, Bart de Laat, Uwe Himmelreich, Guy Bormans, Koen Van Laere
Converging preclinical evidence links extrastriatal dopamine release and glutamatergic transmission via the metabotropic glutamate receptor 5 (mGluR5) to the rewarding properties of alcohol. To date, human evidence is lacking on how and where in the brain these processes occur. Mesocorticolimbic dopamine release upon intravenous alcohol administration and mGluR5 availability were measured in 11 moderate social drinkers by single-session [18 F]fallypride and [18 F]FPEB positron emission tomography, respectively...
May 2018: Addiction Biology
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