S25 * UNITY IN DIVERSITY APSAAR, LASBRA & ESBRA JOINT SYMPOSIUM

Autor: H. Lüddens, B. Birnir, Alfreda Stadlin, R. Camarini, E. Korpi, A. M. Choi Ho, Peter R. Dodd, S.W. Kuo
Rok vydání: 2013
Předmět:
Zdroj: Alcohol and Alcoholism. 48:i25-i26
ISSN: 1464-3502
0735-0414
DOI: 10.1093/alcalc/agt103
Popis: S25.1 GENETIC ASSOCIATIONS AND CRAVING IN ALCOHOLIC IN-PATIENTS {#article-title-2} Background. Relapse is common in alcoholics even after the withdrawal stage has passed. We explored the relationships between alcohol-use history, craving, hormones, personality traits, and gene polymorphisms to identify factors predictive of early relapse. Methods. Alcohol- dependent subjects (n = 193; 60% male) were recruited during a 5-day in-patient detoxification. Global alcohol craving was measured by the Obsessive Compulsive Drinking Scale. Personality traits were assessed on subscales of BIS/BAS, NEO PI-R, and TCI. Subjects reported their state alcohol craving by Alcohol Urge Questionnaire on morning 3–5; samples of saliva and blood were then taken, whilst the subjects were still fasting. Salivary cortisol and plasma leptin and ghrelin levels were quantified by ELISA. Genotyping was performed by PCR-RFLP and High- Resolution Melting. Results. Cluster analysis of the age of onset of heavy drinking identified three groups that differed significantly on various measures, including alcohol consumption and craving. There was a significant negative correlation between ghrelin and craving. Cluster analysis of personality traits identified three distinct profiles in groups that differed significantly on the maintenance of abstinence. The personality profiles of the age-of-onset groups also differed significantly. In female subjects, logistic regression showed that ANNK1 Taq1A, RGS4 SNP7, and COMT rs4646316 were associated with earlier heavy-drinking onset. Conclusions. Our results provide insights for personality-targeted treatments and suggest a possible regulatory role of ghrelin in alcohol craving. Gene polymorphisms that may contribute to the early onset of alcohol misuse were identified. # S25.2 ENVIRONMENTAL ENRICHMENT BLOCKS ETHANOL-INDUCED BEHAVIORAL SENSITIZATION AND DECREASES ETHANOL INTAKE {#article-title-3} Environmental enrichment (EE) is a strategy used to study the environmental influence on the response to addiction-related behaviors. We have demonstrated that EE blocked ethanol-induced sensitization and reduced voluntary ethanol intake in two-bottle choice test. Alterations in the activity of EGR-1 and brain-derived neurotrophic factor (BDNF) in the prefrontal cortex (PFC) have been associated with anxiety-disorders. Mice repeatedly treated with ethanol in EE condition (EE-mice) showed lower expression of ERG-1 and BDNF in the PFC compared to mice housed under standard condition (SC-mice). The reduced expression of ERG-1 and BDNF in response to repeated ethanol found in EE mice seems to be responsible for the reduced behavioral effects of ethanol in EE-mice. CPP is a learning paradigm, which requires associations between reward and environmental cues. Interestingly, EE-mice showed greater ethanol-induced CPP than SC-mice. We have now studied the behavioral consequences of EE in models for the study of stress and anxiety. EE-mice showed lower levels of corticosterone levels after exposure to stress, decreased marble burying and lower latency to open arms entries in the plus-maze when compared to SC-mice. Object recognition test is used to test the spontaneous tendency of rodents to explore a novel object over a familiar, being useful to measure recognition memory process and also motivation. No difference was found in the discrimination ratio between EE and SC-mice, but the exploration score was lower in EE mice than in SC-mice. Our data suggest that EE decreases anxiety-like behavior and the motivation to explore novelty. Financial Support: FAPESP. # S25.3 GABA-A RECEPTORS, ALCOHOL AND RO 15-4513 {#article-title-4} Ethanol has many molecular targets in the brain. One of these targets, studied for a long time, is the γ-aminobutyric acid (GABA) type A receptor, which is expressed as pentameric assembly of various subunits generated from 16-19 different genes. It is also a target for a number of clinically important drugs, which affect the brain networks by promoting synaptic phasic inhibition or by increasing extrasynaptic tonic inhibition. While higher concentrations of ethanol have rather consistently enhanced the GABA-A receptor responses, less clear is whether and how lower, non-intoxicating concentrations affect this receptor. Several hypotheses of subunit combinations sensitive to lower ethanol concentrations have been suggested, but none of them have been widely confirmed. Possible alcohol antagonist effects of the benzodiazepine receptor ligand Ro 15-4513 have repeatedly emerged over the last 15 years, but its mechanisms of action still unsolved. Its efficacy seems to be anyway poor. At the same time, there have been efforts to see whether GABA-A receptor undergoes modulation in the alcoholic brain, using various postmortem brain samples for ligand binding, autoradiography and subunit mRNA quantifications. While these experiments have indicated significant alterations in various properties or levels of GABA-A receptor in alcoholics in brain region-dependent manner, the studies are often too small to give conclusive results. This case report on alcohol and GABA-A receptor encourages to joint efforts for larger scale experiments on the neurochemical effects of alcohol on most interesting target proteins and brain molecular pathways. Supported by the Finnish Foundation for Alcohol Studies. # S25.4 PROFILES OF GABA-A RECEPTOR SUBTYPES IN HUMAN ALCOHOLIC BRAIN {#article-title-5} Purpose. PET imaging of GABAA receptors uses [11C]flumazenil and [11C]Ro15-4513 as tracers. Flumazenil binds to all sites, Ro15-4513 selects α5-containing receptors. Alcoholics show reduced [11C]Ro15-4513 PET signals in hippocampus and accumbens. We determined tracer-binding parameters in autopsy brain. Methods. We used membrane binding to assayradioligandsand modulatorsin five brain regions from alcoholics and matched controls (n = 6). Data were analysed by non-linear curve-fitting. Results. [14C]Flunitrazepam affinity was invariant, [14C]flumazenil affinity varied regionally, and [14C]Ro15-4513 affinity varied both regionally and between groups. [14C]Flunitrazepam and [14C]flumazenil receptor densitieswerehigher in several brain regions of alcoholics,whereas [14C]Ro15-4513 density was not. Zolpidem affinity in modulating [14C]Ro15-4513 and [14C]flumazenil binding was lower in hippocampus and caudate. Regional differences in Hill slope (nH), notably in occipital cortex, precluded a one-site model. Zolpidem modulation of [14C]flumazenil binding resolved into 2 sites in four regions. Affinity waslower in occipital cortex (52 ± 1 µM) than in other regions (range 9–12 µM), P < 0.01, butinvariant across alcoholics and controls. Binding capacities variedregionally but not between case-groups. Zolpidem modulation of [14C]Ro15-4513 bindingresolved into 2 sites in all areas. In controls, the proportion of binding to the high-affinity site was significantly lower in caudate (29%) than in any other region (49–53%); in alcoholics, the fraction differed between hippocampus (27%) and occipital cortex (71%). Regional profiles of binding capacity differed significantly between alcoholics and controls. Conclusions. These data reflectlocal variations in α1 and α5 GABAA subunit expression in alcohol misuse.
Databáze: OpenAIRE
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