***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Although drinking urges and cravings are commonly reported by alcoholics , prospect i ve studies have found inconsistent associations between such urges and drinking relapses . Previous studies have measured drinking urges by use of single-item ratings of alcohol craving or other measures of unknown reliability and validity . To permit improved evaluation of hypotheses regarding alcohol craving , a 49-item question naire that reflects several urge-related domains was developed and pretested . Items assessed subjects ' desire for a drink , expectations of positive effects following drinking , relief of withdrawal and negative affect following drinking , and intention to drink . Exploratory and confirmatory factor analyses of the responses of 351 abstinent , treatment-seeking alcoholics indicated that alcohol urges are best described by a single factor . Based on these analyses , an internally consistent , reliable , and psychometrically valid 8-item scale , the Alcohol Urge Question naire ( AUQ ) , was developed . Data indicated that AUQ scores were strongly related to alcohol dependence severity and to cognitive preoccupation with alcohol , and that they declined with prolonged abstinence . The AUQ may be useful in alcoholism treatment research and in laboratory studies of reactivity to alcohol or other manipulations BACKGROUND Stimuli that are regularly associated with alcohol intake ( AI ) may acquire incentive salience , while other reinforcers can be devalued . We assessed whether brain activation elicited by ( 1 ) alcohol associated , ( 2 ) affectively positive , and ( 3 ) negative versus neutral stimuli is associated with the subsequent risk of relapse . METHODS Twelve detoxified alcoholic subjects ( 6 women and 6 men ) and 12 age-matched and gender-matched healthy control subjects were assessed with functional magnetic resonance imaging ( fMRI ) and a fast single-event paradigm using st and ardized affective and alcohol-associated pictures . Patients were followed for 6 months and AI was recorded . RESULTS In alcoholic subjects , compared with healthy control subjects , ( 1 ) alcohol-related versus neutral visual stimuli elicited increased activation in the prefrontal ( PFC ; BA 6 and 10 ) and cingulate cortex ( BA 23 and 24 ) , precuneus and adjacent parietal cortex ; ( 2 ) positive versus neutral stimuli elicited increased activation in the anterior cingulate cortex ( ACC ; BA 24 ) , PFC ( BA 10 ) , ventral striatum and thalamus ; and ( 3 ) negative versus neutral stimuli elicited increased activation in the PFC ( BA 10 ) . Seven alcoholic subjects relapsed . Within the follow-up period of 6 months , the number of subsequent drinking days ( DD ) and the amount of AI were inversely correlated with brain activation elicited by positive versus neutral stimuli in the thalamus ( DD : r=-0.63 , p=0.03 ; AI : r=-0.63 , p=0.03 ) and in the ventral striatum ( DD : r=-0.60 , p=0.04 ; AI : r=-0.48 , p=0.11 ) . CONCLUSIONS In this study , brain activation elicited by briefly presented alcohol-associated stimuli was not associated with the prospect i ve risk of relapse . Unexpectedly , alcoholic subjects displayed increased limbic brain activation during the presentation of affectively positive but not negative stimuli , which may reflect a protective factor in detoxified alcoholic subjects BACKGROUND Alcoholism represents a major public health issue and treating alcohol dependent patients remains an imminent challenge . Evidence based psychotherapies and pharmacotherapies are available . However , when administered to heterogeneous population s of patients effect sizes are only modest . We present the rationale and design of a double-blind r and omized trial comparing acamprosate , naltrexone , and placebo . Additionally we subtype patients on the basis of biological and psychometric measures and explore their treatment response to both acamprosate and naltrexone . According to our initial hypothesis , the " relief drinker/craver " is an endophenotype associated with glutamatergic dysfunction who responds to acamprosate . The " reward drinker/craver " is mainly associated with alterations in the dopaminergic and opioidergic system and responds to naltrexone . METHODS The study is planned for 430 patients ( 2:2:1 for both drugs and placebo ) over 12 weeks of medication . All receive manualized counselling to improve compliance ( Medical Management ) which is extended to 6 months . Subtyping is primarily done using the acoustic startle reflex , functional magnetic resonance imaging , positron emission tomography ( in a subset of patients ) , and the Inventory of Drinking Situations . Relapsers will be re-r and omized into a second study where additional psychotherapy ( Cognitive Behavioral Intervention ) is used in a stepped care approach . Genotyping and additional analyses such as health economy are being done as well . The study follows the assessment methods , treatments , and medications used in the U.S. based COMBINE study , which will allow for a direct comparison between this U.S. study trial and a study performed in Europe CONTEXT Medication for the treatment of alcoholism is currently not particularly robust . Neuroimaging techniques might predict which medications could be useful in the treatment of alcohol dependence . OBJECTIVE To explore the effect of naltrexone , ondansetron hydrochloride , or the combination of these medications on cue-induced craving and ventral striatum activation . DESIGN Functional brain imaging was conducted during alcohol cue presentation . SETTING Participants were recruited from the general community following media advertisement . Experimental procedures were performed in the magnetic resonance imaging suite of a major training hospital and medical research institute . PATIENTS Ninety non-treatment-seeking alcohol-dependent ( by DSM-IV criteria ) and 17 social drinking ( < 14 drinks per week ) paid volunteers recruited through advertisements at an academic center . INTERVENTIONS A taste of alcohol and a series of alcohol-related pictures , neutral beverage pictures , and visual control images were provided to volunteers after 7 days of double-blind r and omly assigned daily dosing with 50 mg of naltrexone ( n = 23 ) , 0.50 mg of ondansetron hydrochloride ( n = 23 ) , the combination of the 2 medications ( n = 20 ) , or matching placebos ( n = 24 ) . MAIN OUTCOME MEASURES Difference in brain blood oxygen level-dependent magnetic resonance when viewing alcohol pictures vs neutral beverage pictures with a particular focus on ventral striatum activity comparison across medication groups . Self-ratings of alcohol craving . RESULTS The combination treatment decreased craving for alcohol .  Naltrexone with ( P = .02 ) or without ( P = .049 ) ondansetron decreased alcohol cue-induced activation of the ventral striatum .  Ondansetron by itself was similar to naltrexone and the combination in the overall analysis but intermediate in a region-specific analysis . CONCLUSIONS Consistent with animal data that suggest that both naltrexone and ondansetron reduce alcohol-stimulated dopamine output in the ventral striatum , the current study found evidence that these medications , alone or in combination , could decrease alcohol cue-induced activation of the ventral striatum , consistent with their putative treatment efficacy A growing number of imaging studies suggest that alcohol cues , mainly visual , elicit activation in mesocorticolimbic structures . Such findings are consistent with the growing recognition that these structures play an important role in the attribution of incentive salience and the pathophysiology of addiction . The present study investigated whether the presentation of alcohol taste cues can activate brain regions putatively involved in the acquisition and expression of incentive salience . Using functional magnetic resonance imaging , we recorded BOLD activity while delivering alcoholic tastes to 37 heavy drinking but otherwise healthy volunteers . The results yielded a pattern of BOLD activity in mesocorticolimbic structures ( ie prefrontal cortex , striatum , ventral tegmental area/substantia nigra ) relative to an appetitive control . Further analyses suggested strong connectivity between these structures during cue-elicited urge and demonstrated significant positive correlations with a measure of alcohol use problems ( ie the Alcohol Use Disorders Identification Test ) . Thus , repeated exposure to the taste alcohol in the scanner elicits activation in mesocorticolimbic structures , and this activation is related to measures of urge and severity of alcohol problems BACKGROUND In alcohol-dependent patients , alcohol-associated cues elicit brain activation in mesocorticolimbic networks involved in relapse mechanisms . Cue-exposure based extinction training ( CET ) has been shown to be efficacious in the treatment of alcoholism ; however , it has remained unexplored whether CET mediates its therapeutic effects via changes of activity in mesolimbic networks in response to alcohol cues . In this study , we assessed CET treatment effects on cue-induced responses using functional magnetic resonance imaging ( fMRI ) . METHODS In a r and omized controlled trial , abstinent alcohol-dependent patients were r and omly assigned to a CET group ( n = 15 ) or a control group ( n = 15 ) . All patients underwent an extended detoxification treatment comprising medically supervised detoxification , health education , and supportive therapy . The CET patients additionally received nine CET sessions over 3 weeks , exposing the patient to his/her preferred alcoholic beverage .  Cue-induced fMRI activation to alcohol cues was measured at pretreatment and posttreatment . RESULTS Compared with pretreatment , fMRI cue-reactivity reduction was greater in the CET relative to the control group , especially in the anterior cingulate gyrus and the insula , as well as limbic and frontal regions . Before treatment , increased cue-induced fMRI activation was found in limbic and reward-related brain regions and in visual areas . After treatment , the CET group showed less activation than the control group in the left ventral striatum . CONCLUSIONS The study provides first evidence that an exposure-based psychotherapeutic intervention in the treatment of alcoholism impacts on brain areas relevant for addiction memory and attentional focus to alcohol-associated cues and affects mesocorticolimbic reward pathways suggested to be pathophysiologically involved in addiction BACKGROUND The mesocorticolimbic dopamine system is implicated in motivation and reward and may be involved in the development of alcoholism . METHODS We used functional magnetic resonance imaging to study the blood oxygen level-dependent ( BOLD ) response to alcohol-related olfactory stimuli ( AROS ; odors of beer and whiskey ) and non-alcohol-related olfactory stimuli ( NAROS ; odors of grass and leather ) in 10 high-risk ( HR ) drinkers ( average drinks per week , 19.99 ; SD , 6.99 ; all with > or = 2 first- or second-degree alcoholic relatives ) and 5 low-risk ( LR ) social drinking controls ( drinks per week , 2.82 ; SD , 2.87 ; 1 subject had 1 second-degree alcoholic relative ) . Data were analyzed with SPM99 and r and om effects analysis by using regions of interest and corrected cluster statistics ( p < 0.05 ) to focus on the nucleus accumbens ( NAc ) and ventral tegmental area ( VTA ) . RESULTS In HR subjects , there was a greater BOLD signal increase in the NAc during AROS than during clean air . BOLD signal increases during AROS were also greater in the NAc than the signal increases induced by NAROS . The AROS signal was significantly greater than the NAROS signal in a small number of voxels in the VTA . Finally , the AROS/NAROS difference signal was larger in HR drinkers in both the NAc and VTA . CONCLUSIONS Alcoholic olfactory cues may invoke the dopaminergic mesocorticolimbic system to a greater degree than nonalcoholic odors and could be effective tools in exploring the role of the dopamine system in susceptibility to alcoholism Previous studies have indicated that olanzapine decreases craving after a priming dose of alcohol , that craving after a priming dose of alcohol is greater among individuals with the seven-repeat allele of the DRD4 variable number of t and em repeats ( VNTR ) polymorphism , and that the effect of olanzapine ( a D2/D4 antagonist ) is more pronounced among individuals with this allele . The present study tested the hypothesis that olanzapine may be differentially effective at reducing cue-elicited craving and differentially effective as a treatment for alcohol dependence over the course of a 12-week , r and omized , placebo-controlled trial among individuals with and without the seven-repeat allele . Participants who met DSM IV criteria for alcohol dependence were r and omly assigned to receive olanzapine ( 5 mg ) or a placebo over the course of the trial . After 2 weeks of treatment , participants completed a cue reactivity assessment . The results suggested that participants who were homozygous or heterozygous for the seven ( or longer)-repeat allele of the DRD4 VNTR responded to olanzapine with reductions in cue-elicited craving as well as reductions in alcohol consumption over the course of the 12-week trial , whereas individuals with the shorter alleles did not respond favorably to olanzapine BACKGROUND the 14-item Obsessive Compulsive Drinking Scale ( OCDS ) is a quick and reliable self-rating instrument that provides a total and two subscale scores that measure some cognitive aspects of alcohol " craving " . This study vali date d further its utility as an alcoholism severity and treatment outcome instrument . METHODS Alcoholism severity and analogue craving scales were administered at baseline , and the OCDS was given at baseline and weekly to 41 alcohol- 
    Output:
    
As compared to controls , cases demonstrated greater activation of parietal and temporal regions , including posterior cingulate , precuneus and superior temporal gyrus .
Cue-elicited activation of ventral striatum was most frequently correlated with behavioral measures and most frequently reduced by treatment , but these results were often derived from region-of-interest analyses that interrogated only limbic regions .
These findings support long-st and ing theories of mesolimbic involvement in alcohol cue processing , but suggest that cue-elicited activation of other brain areas may more clearly differentiate cases from controls .