bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haloperidol Reduces Stimulant and Reinforcing Effects of Ethanol in Social Drinkers
Authors: Enggasser Justin L. , de Wit Harriet 
Published: April 2006

Background: Despite abundant preclinical support for a role of dopamine (DA) in the stimulant‐like and reinforcing effects of ethanol, there have been few studies directly investigating this mechanism in human subjects. This study examined the effect of a DA antagonist, haloperidol, on the subjective stimulant‐like effects of acute doses of ethanol and on ethanol reinforcement in healthy human volunteers. It was hypothesized that a low dose of the DA D2/D3 antagonist haloperidol (3 mg) would attenuate stimulant‐like subjective effects of ethanol (0.75 g/kg) and reduce the number of drinks chosen during a subsequent choice phase.Methods: Seventeen healthy men and women, 21 to 35 years old, participated in four laboratory sessions conducted at 1‐week intervals. During the four sessions they received, in randomized order under double‐blind conditions, capsules containing haloperidol or placebo followed by three drinks containing ethanol (0.75 g/kg) or placebo, at 30‐min intervals. Subjective and behavioral responses were measured before and after the beverages. After the third beverage, subjects could choose up to five additional doses of the beverage they had ingested.Results: Haloperidol reduced the number of ethanol beverages subjects chose without altering placebo beverage choices. Haloperidol also dampened some of the subjective effects of ethanol, especially in subjects who experienced stimulation after ethanol. Haloperidol reduced stimulant‐like and euphorigenic effects of ethanol in subjects who experienced stimulant effects (n= 8) but had no effect in subjects who did not experience stimulation from ethanol (n= 9).Conclusions: These findings suggest that DA plays a role in the stimulant‐like, euphorigenic, and reinforcing qualities of ethanol in humans. However, the findings also raised new questions about the link between the subjective and reinforcing effects of ethanol.
P300, Disinhibited Personality, and Early‐Onset Alcohol Problems
Authors: Justus Alicia N. , Finn Peter R. , Steinmetz Joseph E. 
Published: April 2006

Background: Recent research suggests that a reduced P300 amplitude of the event‐related potential is associated with a vulnerability to alcoholism. This study tested the hypothesis that reductions in the P300 amplitude would be associated with specific dimensions of disinhibited personality (social deviance proneness and impulsivity) and that these personality traits would mediate the association between P300 and alcohol problems in a young adult sample that varied widely in disinhibitory traits.Methods: Alcohol problems, personality (impulsivity, social deviance, harm avoidance, and excitement seeking), and event‐related potentials were measured in a sample of 190 subjects (87 men, 103 women) with a mean age of 20.7 ± 1.9 years.Results: Social deviance, impulsivity, and alcohol problems were associated with reductions in the P300, but only in male subjects. A structural model suggested that social deviance, impulsivity, and alcohol problems were all strongly related to P300 amplitude at Fz. Further analyses indicated that for male subjects, social deviance mediated the association between P300 at Fz and alcohol problems as well as the association between impulsivity and alcohol problems.Conclusions: This study suggests that reduced P300s are strongly associated with a general tendency toward antisocial, defiant, and impulsive traits, which might, in turn, increase the risk for alcohol abuse. The lack of an association between reduced P300s and personality or alcohol problems in women was unexpected and deserves further study.
Alcohol Availability and Injury: The Role of Local Outlet Densities
Authors: Treno Andrew J. , Gruenewald Paul J. , Johnson Fred W. 
Published: April 2006

Background: We analyzed the relationship between alcohol availability and injury that occurred during the 6 months before survey administration.Method: The data examined were from a general population survey administered to 13,440 California respondents as part of a community‐based project to reduce alcohol‐involved injury and death. Two separate analyses were performed. The first considered individual local outlet densities (which included both on‐premise establishments such as bars and restaurants and off‐premise establishments such as liquor and grocery stores) as they affect individual phone survey respondents’ self‐reported injuries. To address potential spatially autocorrelated errors and geographically lagged effects, a second analysis considered aggregate outlet densities within geographic areas as they affect the proportion of survey respondents who reported injury. No spatial autocorrelation or significant lagged effects were found, which supported our individual‐level analyses.Results: Our analyses indicated an association between both on‐premise and off‐premise individual‐level outlet densities and self‐reported injuries.Conclusion: Alcohol availability seems to be related to self‐reported injury. The mechanisms behind this relationship, however, are not clear, and further study is indicated.
Alcohol Abuse or Dependence Among Mexican American Women Who Report Violence
Authors: Anne Lown E. , Vega William A. 
Published: April 2006

Background: Violence against women has been linked to alcohol disorders in various populations. Few studies have assessed alcohol disorders among assaulted women in a general population of Mexican Americans. This study examined alcohol disorders among Mexican American women who reported physical or sexual assault.Methods: Participants were women (n= 1516, ages 18–59) living in Fresno County, California, who were enrolled in a population‐based, randomized household survey of Mexican‐origin men and women. Crude and adjusted odds ratios (ORs) were calculated for alcohol dependence/abuse (ADA) and physical or sexual assault by a current partner or someone other than a current partner.Results: Women who reported lifetime physical or sexual assault were significantly more likely to meet criteria for ADA (OR = 8.2; 95% confidence interval [CI], 4.4–15.4). After we adjusted for birthplace, age, income, and parental problem drinking, assaulted women were still 4.7 times more likely to meet criteria for ADA (CI, 2.1–10.4). Physical or sexual assault by someone other than a partner was more strongly associated with ADA (OR = 8.7; CI, 4.5–16.9) than assault by a current partner (OR = 3.2; CI, 1.3–7.6). Both physical (OR = 9.0; CI, 4.7–17.0) and sexual assault (OR = 4.7; CI, 2.2–10.0) by either type of perpetrator were associated with ADA.Conclusion: There is a strong association between reporting violence and having a lifetime history of ADA. Although temporal order could not be established, these findings highlight the importance of screening for physical and sexual assault in settings that treat alcohol disorders as well as screening for alcohol disorders among women who seek services related to previous or current violence.
Evidence That the Lore‐1 Region Specifies Ethanol‐Induced Activation in Addition to Sedative/Hypnotic Sensitivity to Ethanol
Authors: Owens Jeremy C. , Bennett Beth , Johnson Thomas E. 
Published: April 2006

Background: Low‐dose ethanol‐induced activation (LDA) and initial sensitivity to alcohol are both predictors of alcohol abuse in human populations. Our hypothesis is that one or more genes specifying hypnotic sensitivity also specify LDA. We tested this hypothesis by using congenic mice derived from the inbred long‐sleep (ILS) and inbred short‐sleep (ISS) strains, which carry an ILS region introgressed onto an ISS background.Methods: LDA was assessed by assigning mice randomly to receive one of five doses of ethanol ranging from 1.2 to 2.4 g/kg. On day 1, animals were injected with saline and placed in a brightly lit activity monitor for 30 min, after which they were returned to their home cages. On day 2, mice were injected with ethanol (20% w/v), their activity was monitored for a 30‐min period, and LDA was determined by subtracting day 1 activity. The blood ethanol concentration of each animal was then assessed at 30 min by retro‐orbital collection of 25 μl of blood.Results: Ethanol had a significant effect on the activity of ISS mice, but ILS mice showed no activation at any dose, similar to the activities of the outbred lines. All three congenic strains were activated at several doses. Lore‐2 and Lore‐5 were not ILS‐like (less active than ISS) at any dose. In contrast, ISS.ILS‐Lore‐1 congenics (carrying an ILS‐derived Lore‐1 allele on the ISS background) were significantly less activated than the ISS controls at 1.8 and 2.4 g/kg of ethanol.Conclusions: The Lore‐2 and Lore‐5 congenic regions do not affect LDA. In contrast, the Lore‐1 congenic region carries one or more genes specifying both initial hypnotic sensitivity to ethanol and LDA.
Does Acetaldehyde Mediate Ethanol Action in the Central Nervous System?
Authors: Mascia Maria Paola , Maiya Rajani , Borghese Cecilia M. , Lobo Ingrid A. , Hara Koji , Yamakura Tomohiro , Gong Diane H. , Beckstead Michael J. 
Published: April 2006

Background: Some of the effects of ethanol in the central nervous system are due to changes in function of ligand‐gated ion channels. Production of detectable amounts of acetaldehyde, a primary metabolite of ethanol, has been demonstrated in brain homogenates. The aim of this study was to determine whether central actions that are often attributed to ethanol may actually be mediated by acetaldehyde.Methods: The effects of acetaldehyde (1–1000 μM) were tested by two‐electrode voltage‐clamp electrophysiology in Xenopus laevis oocytes expressing 10 different ligand‐gated ion channel receptors [α1 glycine; α1β2γ2Sγ‐aminobutyric acid (GABA)A; ρ1 GABAc; 5‐hydroxytryptamine‐3A; NR1a/NR2A NMDA; GluR1/GluR2 AMPA; GluR6/KA2 kainate; and α4β2, α4β4, and α2β4 nicotinic‐acetylcholine] and the G‐protein–coupled inward rectifying potassium channel GIRK2. We also investigated the effect of acetaldehyde on the dopamine transporter (DAT), performing dopamine uptake assays in oocytes expressing DAT.Results: Acetaldehyde (1 and 10 μM) significantly enhanced α1 glycine receptor–mediated currents. Acetaldehyde did not affect the function of any of the other receptors tested or the potassium currents measured in GIRK2 channels. Moreover, acetaldehyde did not alter the DAT‐mediated dopamine uptake.Conclusions: Our results suggest a potential minor role for acetaldehyde in the glycine receptor–mediated effects of ethanol. Otherwise, acetaldehyde does not modulate function of the neuronal receptors tested in this study, in GIRK channels or DAT, when expressed recombinantly in Xenopus laevis oocytes.
Drinking or Abstaining at Age 14? A Genetic Epidemiological Study
Authors: Rose Richard J. , Dick Danielle M. , Viken Richard J. , Pulkkinen Lea , Kaprio Jaakko 
Published: April 2006

Background: Regular drinking by age 14 years is a significant risk factor for alcoholism, and genetically informative data suggest that whether a young adolescent abstains or drinks is largely attributable to familial (or other shared) environmental factors.Methods: Three consecutive birth cohorts of Finnish twins, enrolled into a longitudinal study at age 11 to 12 years, completed a follow‐up questionnaire within 3 months of their 14th birthdays. The sample included 1380 twin sisters and 1330 twin brothers at age 14, and at that age, 35.4% reported using alcohol. Genetic analyses (model‐fitting of twin pair data) and epidemiological analyses (logistical regressions of data from individual twins) were conducted to examine predictive factors of drinking versus abstinence at age 14.Results: Polychoric correlations were substantial across all same‐sex twin pairs but were lower for brother‐sister twins, suggesting significant influences of common environments, with some sex‐specific effects. Common environmental effects were equivalent in male and female adolescents and accounted for 76% of the total variation in abstinence/drinking. Logistical regression analyses among 2206 individual twins with complete data on risk‐relevant measures at both baseline and follow‐up identified significant predictors of drinking or abstaining at age 14, including female sex, twin sibling of the opposite sex, accelerated pubertal development, and the twins’ assessments, made at age 12, of reduced parental monitoring and a less supportive home atmosphere; drinking at age 14 was also predicted by behaviors rated by the twins’ classroom teachers 2 years earlier, increasing with rated behavioral problems but decreasing with rated emotional problems.Conclusions: Our results show that environmental factors shared by twin siblings account for most of the variance in abstaining or drinking at age 14. We identify predictors of drinking in the adolescent twins’ home environments and in their dispositional behaviors, sibling interactions, and pubertal timing.
Naltrexone and Cue Exposure With Coping and Communication Skills Training for Alcoholics: Treatment Process and 1‐Year Outcomes
Authors: Monti Peter M. , Rohsenow Damaris J. , Swift Robert M. , Gulliver Suzy B. , Colby Suzanne M. , Mueller Timothy I. , Brown Richard A. , Gordon Alan , Abrams David B. , Niaura Raymond S. , Asher Marilyn K. 
Published: April 2006

Background: Promising treatments for alcoholics include naltrexone (NTX), cue exposure combined with urge‐specific coping skills training (CET), and communication skills training (CST). This study investigated the effects of combining these elements as treatment adjuncts.Methods: A 2 × 2 design investigated the effects of CET combined with CST, as compared with an education and relaxation control treatment, during a 2‐week partial hospital program (n= 165) followed by 12 weeks of NTX (50 mg/day) or placebo during aftercare (n= 128). Drinking outcomes were assessed at 3, 6, and 12 months after discharge from the partial hospital. Process measures included urge, self‐efficacy (confidence about staying abstinent in risky situations), and self‐reported coping skills. Medically eligible alcohol‐dependent patients were recruited.Results: Among those compliant with medication on at least 70% of days, those who received NTX had significantly fewer heavy drinking days and fewer drinks on days that they drank than those receiving placebo during the medication phase but not during the subsequent 9 months. CET/CST‐condition patients were significantly less likely to report a relapse day and reported fewer heavy drinking days at the 6‐ and 12‐month follow‐ups than patients in the control treatment. Interactions of medication with behavioral treatments were not significant. Process measures showed that NTX resulted in lower weekly urge ratings, and those in CET/CST used more of the prescribed coping skills after treatment, reported fewer cue‐elicited urges, and reported more self‐efficacy in a posttest role‐play test. Drinking reductions at 3, 6, and 12 months correlated with more use of coping skills, lower urge, and higher self‐efficacy.Conclusions: The results suggest the probable value of keeping alcoholics on NTX for longer periods of time and the importance of increasing compliance with NTX. They also support the earlier promising effects of CET and CST as adjuncts to treatment programs for alcoholics by maintaining treatment gains over at least a year. The value of the urge‐specific and general coping skills and of self‐efficacy and urge constructs was demonstrated in their association with drinking outcomes.
Assays for Acetaldehyde‐Derived Adducts in Blood Proteins Based on Antibodies Against Acetaldehyde/Lipoprotein Condensates
Authors: Latvala Jaana , Melkko Jukka , Parkkila Seppo , Järvi Kimmo , Makkonen Kati , Niemelä Onni 
Published: April 2006

Background: Acetaldehyde‐derived protein condensates (adducts) have been suggested as promising biological markers of alcohol abuse because they represent actual metabolites of ethanol. However, the detection of such condensates in vivo has been hampered by a lack of sensitive and specific methods.Methods: To develop new approaches for the detection of acetaldehyde adducts, we have raised antibodies against condensates with acetaldehyde and lipoproteins, which have previously been shown to be readily modified by acetaldehyde in vitro. The characteristics of these antibodies were compared with those raised against bovine serum albumin/acetaldehyde adduct and against other types of lipoprotein modifications, as induced by malondialdehyde, oxidation, and acetylation.Results: The antibodies raised against low‐density lipoprotein (LDL)/acetaldehyde, very low density lipoprotein (VLDL)/acetaldehyde, and bovine serum albumin/acetaldehyde all reacted with protein adducts generated at physiologically relevant concentrations of acetaldehyde in vitro, whereas the antibodies raised against malondialdehyde/LDL, oxidized LDL, or acetylated LDL were not found to cross‐react with the acetaldehyde‐derived adducts. In assays for acetaldehyde adducts from erythrocyte and serum proteins of patients with excessive ethanol consumption (n= 32) and healthy control individuals (n= 22), the antibody prepared against the acetaldehyde/VLDL condensate was found to provide the most effective detection of acetaldehyde adducts in vivo.Conclusions: Current data indicate that acetaldehyde generates immunogenic adducts with lipoproteins in vivo. Antibodies raised against the VLDL/acetaldehyde may provide a basis for new diagnostic assays to examine excessive alcohol consumption.
Regional Specificity Of Ethanol and NMDA Action in Brain Revealed With FOS‐Like Immunohistochemistry and Differential Routes of Drug Administration
Authors: Knapp Darin J. , Braun Christopher J. , Duncan Gary E. , Qian Ying , Fernandes Alda , Crews Fulton T. , Breese George R. 
Published: April 2006

Background: Inhibition of NMDA receptor function in brain is believed to be an important action of ethanol (EtOH). To investigate EtOH inhibition of NMDA receptor responses in vivo, the interaction of these agents in brain after different routes of administration were investigated by using transcription factor Fos protein expression to follow NMDA receptor activation and EtOH inhibition of this response.Methods: The induction of Fos‐like immunoreactivity (Fos‐LI) in 38 regions of the rat brain was measured 2 hr after treatment with NMDA, EtOH, or both. To determine the relative contribution of abdominal drug effects on Fos induction, rats received either intraperitoneal (ip) or intragastric (ig) EtOH and ip or intravenous (iv) NMDA. Rats received EtOH (2.5 g/kg ip or 4 g/kg ig) or vehicle 15 min before NMDA (125 mg/kg ip or 60 mg/kg iv) or vehicle.Results: For the 38 forebrain regions examined, ip and iv NMDA significantly induced Fos‐LI in 13 and 32 regions, respectively. These effects occurred without elicitation of tonic‐clonic seizure activity and were strong after iv NMDA in the frontal, prefrontal, and cingulate cortices, supraoptic nucleus, anterior lateral septum, and dentate gyrus. For EtOH, prominent Fos‐LI induction was found in the central amygdala, dorsolateral bed nucleus of the stria terminalis, Edinger‐Westphal nucleus, and paraventricular hypothalamus. Despite ip and ig EtOH induction of Fos‐LI in these regions, the major effect of EtOH was to block NMDA‐induced Fos‐LI in 8 of 13 (ip) and 27 of 32 (ig) of the NMDA‐positive regions, respectively, including retrosplenial, cingulate, and medial prefrontal cortices, central amygdala, and taenia tecta.Conclusions: These results provide new evidence for the regionally specific functional interactions of EtOH on NMDA receptors in vivo. Moreover, these results support efforts to identify brain region–specific targets for EtOH and EtOH‐induced changes in gene expression.
Effects of Abstinence on the Brain: Quantitative Magnetic Resonance Imaging and Magnetic Resonance Spectroscopic Imaging in Chronic Alcohol Abuse
Authors: O'Neill Joseph , Cardenas Valerie A. , Meyerhoff Dieter J. 
Published: April 2006

Background: Structural brain damage, especially to white matter, is well documented in chronic alcohol abuse. There is also evidence for brain metabolic abnormalities in this condition. It is unknown, however, to what extent these structural and metabolic changes are present in treated alcohol abusers who achieve long‐term abstinence versus treatment‐naïve, heavily drinking individuals.Methods: This study compared 12 recovering alcoholics with 8 actively heavily drinking subjects. Participants underwent magnetic resonance (MR) imaging and proton MR spectroscopic imaging of the brain. Semiautomated image segmentation techniques yielded volumes for gray matter, white matter, white matter lesions, and cerebral spinal fluid in multiple brain regions defined by Talairach stereotaxic coordinates. Automated spectral processing methods yielded gray and white matter concentrations of the metabolites N‐acetylaspartate, creatine, and choline for the same regions.Results: Recovering alcoholics had greater volumes of frontal white matter, but the opposite was true for white matter in a “remainder” region encompassing the basal frontal and temporal lobes, the cerebellum, and the brainstem. Recovering alcoholics also had smaller volumes of white matter lesions in whole brain, in occipital and mesial parietal regions, and in the remainder region. Recovering alcoholics had greater gray matter volumes in the orbital frontal pole and postcentral gyrus, but smaller gray matter volumes in the anterior cingulate. Whole‐brain and regional metabolite concentrations did not differ significantly between the two groups.Conclusions: White and gray matter volumes in different regions of the brain were greater or smaller in recovering, treated alcoholics. The findings suggest region‐specific structural recovery from chronic alcohol–induced brain injury, but also region‐specific long‐term structural damage in abstinent alcoholics. White matter lesions were widespread in active drinkers and may partly resolve during long‐term abstinence. Proton MR spectroscopic measures, as applied in this cross‐sectional study, were largely ineffective in revealing metabolic effects of abstinence on the alcohol‐damaged brain.