Beyond genome ‐wide significance: integrative approaches to the interpretation and extension of GWAS findings for alcohol use disorder
Abstract
Alcohol use disorder (AUD) is a heritable complex behavior. Due to the highly polygenic nature of AUD, identifying genetic variants that comprise this heritable variation has proved to be challenging. With the exception of functional variants in alcohol metabolizing genes (e.g. ADH1B and ALDH2), few other candidate loci have been confidently linked to AUD. Genome‐wide association studies (GWAS) of AUD and other alcohol‐related phenotypes have either produced few hits with genome‐wide significance or have failed to replicate on further study. These issues reinforce the complex nature of the genetic underpinni...
Source: Addiction Biology - November 1, 2017 Category: Addiction Authors: Jessica E. Salvatore, Shizhong Han, Sean P. Farris, Kristin M. Mignogna, Michael F. Miles, Arpana Agrawal Tags: Original Article Source Type: research
Validation of a behavioral economic purchase task for assessing drug abuse liability
Abstract
Behavioral economic purchase tasks quantify drug demand (i.e. reinforcing value of a drug) and have been used extensively to assess the value of various drugs among current users. However, purchase tasks have been rarely used with unfamiliar drugs to address a compound's abuse liability, and the current study sought to validate the paradigm in this capacity. Using a double‐blind placebo‐controlled within‐subjects drug challenge design, the study evaluated differential drug demand on an experimental drug purchase task for a 20 mg dose of oral D‐amphetamine (versus placebo), a prototypic psychostimulant, in...
Source: Addiction Biology - November 1, 2017 Category: Addiction Authors: James MacKillop, Nicholas I. Goldenson, Matthew G. Kirkpatrick, Adam M. Leventhal Tags: Original Article Source Type: research
Appetitive to aversive counter ‐conditioning as intervention to reduce reinstatement of reward‐seeking behavior: the role of the serotonin transporter
Abstract
Counter‐conditioning can be a valid strategy to reduce reinstatement of reward‐seeking behavior. However, this has not been tested in laboratory animals with extended cocaine‐taking backgrounds nor is it well understood, which individual differences may contribute to its effects. Here, we set out to investigate the influence of serotonin transporter (5‐HTT) genotype on the effectiveness of counter‐conditioning after extended access to cocaine self‐administration. To this end, 5‐HTT+/+ and 5‐HTT−/− rats underwent a touch screen‐based approach to test if reward‐induced reinstatement of respon...
Source: Addiction Biology - November 1, 2017 Category: Addiction Authors: Peter Karel, Amanda Almacellas ‐Barbanoj, Jeffrey Prijn, Anne‐Marije Kaag, Liesbeth Reneman, Michel M.M. Verheij, Judith R. Homberg Tags: Original Article Source Type: research
Methamphetamine binge administration dose ‐dependently enhanced negative affect and voluntary drug consumption in rats following prolonged withdrawal: role of hippocampal FADD
This study evaluated the long‐term consequences of binge methamphetamine administration (three pulses/day, every 3 hours, 4 days, i.p.; dose–response: 2.5, 5 and 7.5 mg/kg) in adult Sprague–Dawley rats at two behavioral levels following 25 days of withdrawal: (1) negative affect (behavioral despair—forced‐swim test, and anhedonia—1% sucrose consumption, two‐bottle choice test) and (2) voluntary methamphetamine consumption (20 mg/l, two‐bottle choice test). Striatal and hippocampal brain samples were dissected to quantify monoamines content by high‐performance liquid chromatography and to evaluate neu...
Source: Addiction Biology - November 1, 2017 Category: Addiction Authors: Rub én García‐Cabrerizo, M. Julia García‐Fuster Tags: Original Article Source Type: research
Extinction and reinstatement of an operant responding maintained by food in different models of obesity
In this study, we used an operant paradigm of food‐seeking behavior on two different diet‐induced obesity models, a free‐choice chocolate‐mixture diet and a high‐fat diet with face validity for a rapid development of obesity or for unhealthy food regularly consumed in our societies. A reduced operant performance and motivation for the hedonic value of palatable chocolate pellets was revealed in both obesity mouse models. However, only mice exposed to high‐fat diet showed an increased compulsive‐like behavior in the absence of the reinforcer further characterized by impaired operant learning, enhanced impulsiv...
Source: Addiction Biology - November 1, 2017 Category: Addiction Authors: Aurelijus Burokas, Elena Mart ín‐García, Jose Espinosa‐Carrasco, Ionas Erb, Jerome McDonald, Cedric Notredame, Mara Dierssen, Rafael Maldonado Tags: Original Article Source Type: research
Rich club and reward network connectivity as endophenotypes for alcohol dependence: a diffusion tensor imaging study
Abstract
We aimed to examine the whole‐brain white matter connectivity and local topology of reward system nodes in patients with alcohol use disorder (AUD) and unaffected siblings, relative to healthy comparison individuals. Diffusion‐weighted magnetic resonance imaging scans were acquired from 18 patients with AUD, 15 unaffected siblings of AUD patients and 15 healthy controls. Structural networks were examined using network‐based statistic and connectomic analysis. Connectomic analysis showed a significant ordered difference in normalized rich club organization (AUD < Siblings < Controls). We also found ...
Source: Addiction Biology - November 1, 2017 Category: Addiction Authors: Nabi Zorlu, Necip Çapraz, Esra Oztekin, Başak Bagci, Maria A. Di Biase, Andrew Zalesky, Fazıl Gelal, Emre Bora, Ercan Durmaz, Lütfullah Beşiroğlu, Aybala Sarıçiçek Tags: Original Article Source Type: research
Rat brain CYP2D activity alters in vivo central oxycodone metabolism, levels and resulting analgesia
Abstract
Oxycodone is metabolized by CYP2D to oxymorphone. Despite oxymorphone being a more potent opioid‐receptor agonist, its contribution to oxycodone analgesia may be minor because of low peripheral production, low blood–brain barrier permeability and central nervous system efflux. CYP2D metabolism within the brain may contribute to variation in central oxycodone and oxymorphone levels, thereby affecting analgesia. Brain CYP2D expression and activity are subject to exogenous regulation; nicotine induces rat brain, but not liver, CYP2D consistent with higher brain CYP2D in smokers. We assessed the role of rat brain ...
Source: Addiction Biology - November 1, 2017 Category: Addiction Authors: Douglas M. McMillan, Sharon Miksys, Rachel F. Tyndale Tags: Original Article Source Type: research
Neurological, nutritional and alcohol consumption factors underlie cognitive and motor deficits in chronic alcoholism
We examined neurological and nutritional factors as possible contributors to heterogeneity in impairment. Participants with ALC (n = 96) and a normal comparison group (n = 41) were examined on six cognitive and motor domains. Signs of historically determined subclinical Wernicke's encephalopathy were detected using the Caine et al. criteria, which were based on postmortem examination and chart review of antemortem data of alcoholic cases with postmortem evidence for Wernicke's encephalopathy. Herein, four Caine criteria provided quantification of dietary deficiency, cerebellar dysfunction, low general cognitive functio...
Source: Addiction Biology - November 1, 2017 Category: Addiction Authors: Rosemary Fama, Anne ‐Pascale Le Berre, Cheshire Hardcastle, Stephanie A. Sassoon, Adolf Pfefferbaum, Edith V. Sullivan, Natalie M. Zahr Tags: Original Article Source Type: research
Quantitative evaluation of cue ‐induced reinstatement model for evidence‐based experimental optimization
Abstract
Cue‐induced reinstatement is a widely used model for investigating relapse of reward‐seeking behavior with high face validity in relation to clinical observations. Yet, face validity is not sufficient to evaluate an animal model, and quantitative, evidence‐based analysis is required to estimate the ultimate applicability of this paradigm. Furthermore, such analysis would allow an accurate and reproducible design of future experiments. Here, we conducted meta‐analysis and cluster analysis to characterize the impact of cue type (visual, auditory, olfactory or combinations thereof), intensity (e.g. light freq...
Source: Addiction Biology - November 1, 2017 Category: Addiction Authors: Julia Oberhofer, Hamid R. Noori Tags: Original Article Source Type: research
Activation of glucagon ‐like peptide‐1 receptors in the nucleus accumbens attenuates cocaine seeking in rats
Abstract
Recent evidence indicates that activation of glucagon‐like peptide‐1 (GLP‐1) receptors reduces cocaine‐mediated behaviors and cocaine‐evoked dopamine release in the nucleus accumbens (NAc). However, no studies have examined the role of NAc GLP‐1 receptors in the reinstatement of cocaine‐seeking behavior, an animal model of relapse. Here, we show that systemic infusion of a behaviorally relevant dose of the GLP‐1 receptor agonist exendin‐4 penetrated the brain and localized with neurons and astrocytes in the NAc. Administration of exendin‐4 directly into the NAc core and shell subregions signifi...
Source: Addiction Biology - November 1, 2017 Category: Addiction Authors: Nicole S. Hernandez, Bernadette O'Donovan, Pavel I. Ortinski, Heath D. Schmidt Tags: Original Article Source Type: research
Central administration of galanin N ‐terminal fragment 1–15 decreases the voluntary alcohol intake in rats
We describe for the first time that GAL(1–15), via central mechanisms, induces a strong reduction in preference and ethanol consumption in rats. These effects were significantly different than GAL. GAL receptor (GALR) 2 was involved in these effects, because the specific GALR2 antagonist M871 blocked GAL(1–15) mediated actions in preference and ethanol intake. Importantly, the mechanism of this action involves changes in GALR expression and also in immediate‐early gene C‐Fos and receptors‐internalization‐related gene Rab5 in the striatum. The relevance of the striatum as a target for GAL(1–15) was supported b...
Source: Addiction Biology - November 1, 2017 Category: Addiction Authors: Carmelo Mill ón, Antonio Flores‐Burgess, Estela Castilla‐Ortega, Belén Gago, María García‐Fernandez, Antonia Serrano, Fernando Rodriguez de Fonseca, José Angel Narváez, Kjell Fuxe, Luis Santín, Zaida Díaz‐Cabiale Tags: Original Article Source Type: research
Neuropeptide CART prevents memory loss attributed to withdrawal of nicotine following chronic treatment in mice
Abstract
Although chronic nicotine administration does not affect memory, its withdrawal causes massive cognitive deficits. The underlying mechanisms, however, have not been understood. We test the role of cocaine‐ and amphetamine‐regulated transcript peptide (CART), a neuropeptide known for its procognitive properties, in this process. The mice on chronic nicotine treatment/withdrawal were subjected to novel object recognition task. The capability of the animal to discriminate between the novel and familiar objects was tested and represented as discrimination index (DI); reduction in the index suggested amnesia. Nicot...
Source: Addiction Biology - November 1, 2017 Category: Addiction Authors: Chandrashekhar D. Borkar, Sneha Sagarkar, Amul J. Sakharkar, Nishikant K. Subhedar, Dadasaheb M. Kokare Tags: Original Article Source Type: research
Increased plasma oleoylethanolamide and palmitoleoylethanolamide levels correlate with inflammatory changes in alcohol binge drinkers: the case of HMGB1 in women
Abstract
Alcohol binge drinking is a heavy pattern of alcohol consumption increasingly used by young people. In a previous study, we reported that young drinkers with a 2‐year history of binge alcohol consumption had an overactivation of the innate immune system and peripheral inflammation when compared with controls. In the present study, we measured several biolipids that are fatty acid derivatives belonging to the acylethanolamide or 2‐acylglycerol families in the plasma of the same subjects (n = 42; 20 men and 22 women). We found that during abstinence, alcohol binge drinkers had elevated plasma levels of oleoyle...
Source: Addiction Biology - November 1, 2017 Category: Addiction Authors: Mar ía Antón, Alicia Rodríguez‐González, Inmaculada Concepción Rodríguez‐Rojo, Antoni Pastor, Ángeles Correas, Antonia Serrano, Antonio Ballesta, Francisco Alén, Raquel Gómez de Heras, Rafael Torre, Fernando Rodríguez de Fonseca, Laura Orio Tags: Special Issue Source Type: research
N ‐Methyl‐d‐aspartate receptor co‐agonist availability affects behavioral and neurochemical responses to cocaine: insights into comorbid schizophrenia and substance abuse
Abstract
Both schizophrenia (SZ) and substance abuse (SA) exhibit significant heritability. Moreover, N‐methyl‐d‐aspartate receptors (NMDARs) have been implicated in the pathophysiology of both SZ and SA. We hypothesize that the high prevalence of comorbid SA in SZ is due to dysfunction of NMDARs caused by shared risk genes. We used transgenic mice with a null mutation of the gene encoding serine racemase (SR), the enzyme that synthesizes the NMDAR co‐agonist d‐serine and an established risk gene for SZ, to recreate the pathology of SZ. We determined the effect of NMDAR hypofunction resulting from the absence of ...
Source: Addiction Biology - November 1, 2017 Category: Addiction Authors: Matthew D. Puhl, Rajeev I. Desai, Shunsuke Takagi, Kendall T. Presti, Michelle R. Doyle, Rachel J. Donahue, Samantha M. Landino, Jack Bergman, William A. Carlezon, Joseph T. Coyle Tags: Original Article Source Type: research
Working memory predicts methamphetamine hair concentration over the course of treatment: moderating effect of impulsivity and implications for dual ‐systems model
Abstract
High impulsivity and poor executive function are characteristic of methamphetamine use disorder. High arousal in the impulsive system has been proposed to compromise the executive system's regulating ability (i.e. the dual‐systems model). While interaction between these variables may partly explain poor treatment outcomes associated with methamphetamine use disorder, previous research has tended to examine each factor separately. We investigated whether high impulsivity (measured with an impulsive choice task) and poor executive function (measured with a working memory task) predict methamphetamine use (determin...
Source: Addiction Biology - November 1, 2017 Category: Addiction Authors: Adam J. Rubenis, Rebecca E. Fitzpatrick, Dan I. Lubman, Antonio Verdejo ‐Garcia Tags: Original Article Source Type: research
