bluuebunny/crossref_metadata_2025_split huggingface dataset:
Naltrexone Suppresses Ethanol Intake in 6‐Hydroxydopamine–Treated Rats
Authors: Koistinen Meri , Tuomainen Päivi , Hyytiä Petri , Kiianmaa Kalervo 
Published: April 2006

Background: The suppressive effect of opioid antagonists, such as naltrexone, on ethanol intake has been suggested to be based on the interference with ethanol‐induced stimulation of dopamine release in the nucleus accumbens. The aim of this study was to determine whether reduction of dopamine innervation to the nucleus accumbens with the neurotoxin 6‐hydroxydopamine (6‐OHDA) alters naltrexone‐induced suppression of ethanol consumption. Because the mesolimbic dopaminergic neurons have also been implicated in ethanol reinforcement, the effects of 6‐OHDA on the maintenance and acquisition of ethanol intake were also studied.Methods: To damage accumbal terminals of the mesolimbic dopamine neurons, alcohol‐preferring Alko Alcohol (AA) rats were given bilateral injections of 6‐OHDA or vehicle into the nucleus accumbens after pretreatment with desipramine and pargyline. The effect of the lesion on the acquisition or maintenance of ethanol self‐administration was studied in animals having continual access to ethanol solution (10% v/v) and water. Subsequently the effect of naltrexone on ethanol consumption was determined.Results: Naltrexone (0.03–3.0 mg/kg subcutaneously) suppressed ethanol consumption in a dose‐dependent manner both in 6‐OHDA–treated and control animals given a daily 90‐min access to ethanol solution. When the rats had continual access to ethanol, there was a clear day‐to‐day decline in ethanol intake during the first 5 days of the 7‐day naltrexone treatment (10 mg/kg subcutaneously). 6‐OHDA treatment had no effect on either the acquisition or maintenance of ethanol self‐administration. Postmortem analysis of the brain dopamine content revealed approximately 92% depletion of dopamine in the nucleus accumbens of the 6‐OHDA–treated rats.Conclusions: The suppressive effect of naltrexone does not depend on naltrexone's interaction with dopaminergic terminals in the nucleus accumbens. Furthermore, the role of the mesolimbic dopamine pathway is probably not central either in the acquisition or maintenance of ethanol self‐administration in alcohol‐preferring AA rats.
Genetic Selection for High and Low Alcohol Consumption in a Limited‐Access Paradigm
Authors: Lê A. D. , Israel Y. , Juzytsch W. , Quan B. , Harding S. 
Published: April 2006

Background: Several rat lines have been bred for their differences in alcohol consumption based on a continuous‐access paradigm in which alcohol solution is available 24 hr/day. The limited‐access paradigm (LAP), in which access to alcohol solution is restricted to a short period per day, however, has been used extensively to investigate the neurochemical mechanisms underlying alcohol consumption. There is evidence of possible differences in genetic determination of alcohol drinking in a continuous‐ versus limited‐access condition. For these reasons, selective breeding for high‐ and low‐alcohol consumption (HARF and LARF, respectively) based on a LAP was conducted.Methods: N/Nih rats were used as the breeding stock. A within‐family breeding procedure was used to develop HARF and LARF lines with 10 families per line. Access to alcohol solution was restricted to 20 min/day. Alcohol was provided as 3%, 6% and 12% w/v solutions. Average intake of alcohol during the 12% phase was used as the selection criterion. Inbreeding began in the seventh generation.Results: After the sixth generation of selection, rats from the HARF line consumed an average of 1.2 g/kg, whereas rats from the LARF line consumed an average of 0.6 g/kg of alcohol during the 20‐min access period. Alcohol consumption remained stable over the next eight generations of inbreeding. In the continuous‐access‐drinking paradigm, the HARF and LARF rats consumed an average of 5.5 to 7.0 g/kg and 1.0 to 2.0 g/kg of alcohol per day respectively. An estimated heritability of 0.25 was obtained.Conclusions: These findings indicate that alcohol drinking in the LAP is influenced by genetic factors. Differences in alcohol drinking in the LAP also generalize to continuous access drinking. These rat lines will be very useful for investigations into the genetic and neurochemical mechanisms underlying alcohol drinking.
The Role of Alcohol in Accident and Violent Deaths in Finland
Authors: Lunetta Philippe , Penttilä Antti , Sarna Seppa 
Published: April 2006

Background: In Finland, the high rates of forensic autopsy and postmortem toxicology furnish a reliable base for nation‐wide studies on alcohol‐related violent deaths.Material and Methods: National mortality and population data within Finland, from 1987 to 1996, were used to analyze sex‐ and age‐specific rates, proportions, and trends of violent deaths associated with alcohol. Deaths were defined as alcohol‐related when alcohol was certified as a contributing factor to death.Results: During the study period, 10,360 (23.3%) of the 45,544 violent deaths that occurred were alcohol‐related. Among 15‐ to 64‐year‐olds, 28.6% of accidents, 30.5% of suicides, and 55.3% of homicides were associated with alcohol (alcohol‐positive). Differences in epidemiologic patterns and trends for different types of violent death were observed between sexes and age groups. For instance, alcohol‐positive accidents significantly decreased in males (−2.3%/year; CL95: −3.3, −1.2;p < 0.001), but not in females (+0.5%/year; CL95: −2.7, +3.7;p= 0.772), and alcohol‐positive suicides increased slightly in females (+3.9%/year; CL95: +0.0, +7.9;p= 0.047), but not in males (−0.2%/year, CL95: −1.4, +1.0;p= 0.704).Conclusions: The victims of violent deaths have often consumed or abused alcohol before the fatal events. Especially in young adults, consumption of alcohol is likely one of the most serious risk factors in accidents and may decrease the threshold for suicide ideation and impulsive behaviors. Studies that explore the effects of sociodemographic and health factors on random populations with relevant control data will increase the understanding of the causal connection between alcohol and violent deaths.
Confirmation of Correlations and Common Quantitative Trait Loci Between Neurotensin Receptor Density and Hypnotic Sensitivity to Ethanol
Authors: Erwin V. Gene , Gehle Vaughn M. , Davidson Kirsten , Radcliffe Richard A. 
Published: April 2006

Background: In previous studies, genetic correlations were observed between hypnotic sensitivity to ethanol and high‐affinity neurotensin receptor (NTS1) binding. Provisional quantitative trait loci (QTLs) were identified for these traits, and some of these QTLs were found on common chromosomal regions. In continued efforts to examine the relationship between NTS1 binding capacity and hypnotic sensitivity to ethanol, studies were designed to confirm correlations between NTS1 densities in the brain, duration of ethanol‐induced loss of righting reflex (LORR), and blood ethanol concentrations at regain of righting reflex (BECRR). Another purpose of the study was to confirm QTLs for these traits.Methods: ILS X ISS F 2 mice and HAS X LAS F 2 rats as well as the progenitors were tested for LORR, BECRR, and NTS1 densities. Phenotypic correlations were calculated between LORR and BECRR and between these measures and NTS1 densities in striatum from both mice and rats. The F 2 mice were genotyped by using polymorphic markers for five previously reported QTLs for LORR to confirm QTLs for BECRR and NTS1 densities in striatum, ventral midbrain, and frontal cortex.Results: Phenotypic correlations were found between LORR and BECRR (r=−0.66 to −0.74, p < 10−9) and between these measures and NTS1 densities in striatum (r= 0.28–0.38, p < 10−2) from both mice and rats. QTLs for LORR and BECRR (lod score = 2–6) were found in common regions of chromosomes 1, 2, and 15. By using the combined results from a previous LSXSS RI study and the current results, a suggestive QTL (lod score = 3.1) for striatal NTS1 receptor densities was found on chromosome 15 at approximately 60 cM, in the same region as the chromosome 15 LORR/BECRR QTL.Conclusions: The results are in agreement with previously reported correlations and QTLs for NTS1 receptor densities and measures of hypnotic sensitivity to ethanol in mice and extend those correlations to another species, the rat. These findings support a role for NTS1 in genetically mediated differences in hypnotic sensitivity to ethanol.
Classification and Course of Alcohol Problems Among Adolescents in Addictions Treatment Programs
Authors: Chung Tammy , Martin Christopher S. 
Published: April 2006

Background: This study tested whether adolescents in addictions treatment programs could be reliably classified into milder and more severe alcohol problem categories using latent class analysis, and examined the relation of latent class structure to DSM‐IV alcohol diagnoses. Transition probabilities among the latent classes at 1‐year follow‐up and their predictors were used to characterize the short‐term course of alcohol problems.Methods: Adolescents recruited from addictions treatment were administered a modified section of the Structured Clinical Interview for the DSM (SCID) alcohol use disorders (AUD) during or shortly after addictions treatment and at 1‐year follow‐up. DSM‐IV lifetime conduct disorder diagnosis was assessed at baseline using a modified version of the Schedule for Affective Disorders and Schizophrenia for School‐Age Children (K‐SADS).Results: A 3‐class solution that represented increasing severity of alcohol problems (i.e., asymptomatic, mild, and severe) provided the best fit to the alcohol symptom data, and was consistent across gender, ethnicity, and presence of conduct disorder. Cross‐classification of latent class membership with DSM‐IV alcohol diagnosis indicated only a fair level of agreement. There was an overall decrease in alcohol problem severity from baseline to follow‐up. Conditional transition probabilities indicated that males and those with conduct disorder, particularly for those in the severe class at baseline, had a lower likelihood of transitioning to the asymptomatic class at 1‐year follow‐up.Conclusions: The latent class structure of alcohol problems in an adolescent clinical sample was best represented by a 3‐class severity‐based model. Cross‐classification of latent class membership with DSM‐IV alcohol diagnosis suggests the potential utility of re‐organizing diagnostic criteria to better distinguish the relative severity of abuse and dependence diagnoses. Transitions between latent classes were fairly common at 1‐year follow‐up, and characterized by a general reduction in alcohol symptoms.
An Examination Between Single‐Parent Family Background and Drunk Driving in Adulthood: Findings From The Northern Finland 1966 Birth Cohort
Authors: Sauvola Anu , Miettunen Jouko , Järvelin Marjo‐Riitta , Räsänen Pirkko 
Published: April 2006

Background: It has been suggested earlier that parental loss could be an important risk factor for alcoholism in adulthood. We e‐plored the association between different types of childhood families with later alcohol‐related problems of the offspring, in particular drunk driving.Methods: We used a large, prospectively collected general population birth cohort database (n= 10,934), the Northern Finland 1966 Birth Cohort. Linked with the National crime register, it provided information on drunk driving offenses known to the police that involved persons 15 to 32 years of age (n= 432). Type of family was categorized into five subgroups: two‐parent family and four types of single‐parent families (single‐parent all the time, single‐parent at birth, parental death, parental divorce). The information about family type was obtained from questionnaires given to the mothers during mid‐pregnancy and at the time of the 14‐year follow‐up.Results: Single‐parent family during childhood significantly increased the risk of drunk driving in adulthood among both males and females. Males who were born in single‐mother families were at the highest risk of drunk driving offenses in adulthood (adjusted OR 2.4; 95% CI 1.4–4.2). The association between single‐parent family and drunk driving among males was seen in all types of single‐parent families e‐cept for parental death.Conclusions: Results suggest that growing up in a single‐parent family is a potentially powerful predictor of adult alcohol‐related problems, i.e., early‐onset, late‐onset, and recidivistic drunk driving.
Concurrent Alcoholism and Social Anxiety Disorder: A First Step Toward Developing Effective Treatments
Authors: Randall Carrie L. , Thomas Suzanne , Thevos Angelica K. 
Published: April 2006

Background: Social an‐iety disorder (also called social phobia) is an an‐iety disorder in which affected individuals fear the scrutiny of others. Clinical reports suggest that individuals with social an‐iety disorder often use alcohol to alleviate an‐iety symptoms, a practice that leads to alcohol abuse and/or dependence in appro‐imately 20% of affected individuals. The present study investigated whether simultaneous treatment of social phobia and alcoholism, compared with treatment of alcoholism alone, improved alcohol use and social an‐iety for clients with dual diagnoses of social an‐iety disorder and alcohol dependence.Methods: The design was a two‐group, randomized clinical trial that used 12 weeks of individual cognitive behavioral therapy for alcoholism only (n= 44) or concurrent treatment for both alcohol and social anxiety problems (n= 49). Outcome data were collected at the end of 12 weeks of treatment and at 3 months after the end of treatment.Results: Results with intent‐to‐treat analyses showed that both groups improved on alcohol‐related outcomes and social an‐iety after treatment. With baseline scores covaried, there was a significant effect of treatment group on several drinking measures. Counter to the hypothesis, the group treated for both alcohol and social an‐iety problems had worse outcomes on three of the four alcohol use indices. No treatment group effects were observed on social an‐iety indices.Conclusions: Implications for the staging of treatments for coe‐isting social phobia and alcoholism are discussed, as well as ways that modality of treatments might impact outcomes.
Identification of Heavy Drinkers By Using the Early Detection of Alcohol Consumption Score
Authors: Harasymiw James W. , Bean Pamela 
Published: April 2006

Background: The objective of this study was to evaluate the use of routine blood chemistry and hematology tests to detect heavy drinkers among ambulatory subjects. Heavy drinkers were defined as subjects who consumed an average of four or more standard drinks per day if male and an average of three or more standard drinks per day if female, for at least 1 month before sample collection (1 standard drink = 15 ml of absolute ethanol).Methods: A routine blood chemistry panel and the demographic factors of age, sex, and ethnicity were evaluated by using linear discriminant function (LDF) analysis to classify subjects as heavy drinkers or light drinkers. The classification was validated by comparison with drinking patterns established by standardized questionnaire and interview. Subjects (n= 807) were males and females with known drinking patterns recruited from 25 centers that included detoxification and rehabilitation institutions, churches, and community groups in the Milwaukee and Boston areas.Results: With LDF, 88% of the heavy drinkers and 92% of the light drinkers were correctly identified by the Early Detection of Alcohol Consumption test. The LDF performed the best when used to identify heavy drinking in ages 40 and above, a group that showed 84% (120 of 143) sensitivity at 97% (152 of 157) specificity. Performance in females showed 73% (76 of 104) sensitivity at 94% (129 of 137) specificity, rates higher than obtained with any single biochemical marker previously examined. Receiver operating characteristic plot analysis showed areas under the curve of 0.94 for females and 0.95 for males (p < 0.0001).Conclusions: The Early Detection of Alcohol Consumption score is a practical laboratory screen for detecting heavy drinking based on blood constituents ordered routinely in clinical settings.
A Genome‐Wide Search for Genes That Relate to a Low Level of Response to Alcohol
Authors: Schuckit M. A. , Edenberg H. J. , Kalmijn J. , Flury L. , Smith T. L. , Reich T. , Bierut L. , Goate A. , Foroud T. 
Published: April 2006

Background: The low level of response (LR) to alcohol is genetically influenced in both humans and animals, and a low LR is a characteristic of offspring of alcoholics that has been reported to predict alcoholism 10 and 15 years later. The genes that contribute to a low LR have not yet been identified.Methods: A 12‐item questionnaire that measures LR, the Self Rating of the Effects of Alcohol (SRE) instrument, was filled out by 745 individuals from the Collaborative Study on the Genetics of Alcoholism (COGA) for whom genetic material was available. These subjects were genotyped by using 336 markers with an average heterozygosity of 0.74 and an average intermarker distance of 10.5 cM. Both quantitative and qualitative nonparametric, sib‐pair analyses were carried out for the SRE measure related to early drinking experiences.Results: Correlations of SRE scores across related individuals were significant and between 0.16 and 0.22 for most values, compared with nonsignificant correlations of 0.03 or less among unrelated individuals. Linkage analyses performed by using the FIRST 5 variables (first five times alcohol is consumed) identified four chromosomal regions with lod scores ≥2.0 whose maximum was also near a marker. One of these chromosomal regions previously was linked to alcohol dependence in the COGA sample.Conclusions: These data document the familial nature of a low LR to alcohol as measured by the SRE and suggest several chromosomal regions that might contribute to the phenomenon.
Mismatch Negativity in Subjects at High Risk for Alcoholism
Authors: Lei Zhang Xiao , Cohen Howard L. , Porjesz Bernice , Begleiter Henri 
Published: April 2006

Background: Evidence from P300 studies in both alcohol‐dependent and high‐risk (HR) individuals suggests that the reduced P300 amplitudes that often characterize these individuals may reflect a deficit in inhibition (hyperexcitability) in the central nervous system. In this context, the mismatch negativity (MMN) was investigated in the male and female HR offspring of alcohol‐dependent fathers and a mixed‐sex, low‐risk (LR) control group.Methods: As subjects read popular materials, they received a random sequence of 500 binaurally presented tones of 600 Hz and 1600 Hz. The designation of the rare stimulus (n= 60 trials) and frequent stimulus (n= 440 trials) was alternated across subjects.Recordings of MMN were made from 61 electrodes; risk group comparisons were restricted to the five frontal midline electrodes: Fpz, Afz, Fz, Fcz, and Cz. The MMN was obtained by calculating the integral of the area under the curve for both the frequent and rare waveforms over an interval from 100 to 190 msec and then subtracting the former from the latter.Results: The primary observation was that MMN responses in the HR group were significantly larger than those in the LR group. In addition, both LR and HR individuals manifested differential responses to the rare and frequent stimuli, and MMN responses in both groups were largest at Fcz and smallest at Fpz.Discussion: The results indicate that individuals at high risk for alcoholism differ electrophysiologically from LR controls. These differences were manifested as larger magnitudes of the MMN. The findings suggest the possibility that as measured by the MMN, individuals at high risk for alcoholism may be characterized by a deficit in inhibition (excessive neural excitation). The presence of these preexisting central nervous system states may lead to ethanol use for self‐medication, which then may facilitate the development of both tolerance to and dependence on ethanol.
Serotonergic Dysfunction, Negative Mood States, and Response to Alcohol
Authors: Heinz Andreas , Mann Karl , Weinberger Daniel R. , Goldman David 
Published: April 2006

Background: Dysfunction of central serotonergic neurotransmission has been implicated in the pathogenesis and maintenance of alcoholism. Serotonergic dysfunction may be associated with three behavior patterns relevant for alcoholism: impulsive aggression, negative mood states, and a low response to alcohol intake.Methods: We reviewed the literature on the psychopathological correlates of serotonergic dysfunction and focused on studies that assess the interaction between negative mood states and alcohol response.Results: Prospective studies in nonhuman primates that underwent early separation stress found an association between a low serotonin turnover rate and the disposition to excessive alcohol intake and impulsive aggression. These findings seem to be relevant for a subgroup of alcoholics with a low serotonin turnover rate and antisocial personality traits. Cross‐sectional data in humans also support a relationship between reduced serotonergic neurotransmission and aggressive behavior and indicate that the association of serotonergic dysfunction and aggression may be mediated by negative mood states. This hypothesis is in accordance with a large body of data linking anxiety and depression to serotonergic dysfunction. In human alcoholics, brain imaging has detected a reduction in serotonin transporter availability in association with depression. Serotonin transporter availability seems to be related to reduced GABA‐ergic sedation and the acute response to alcohol intake, an important predictor of subsequent development of alcohol dependence.Conclusions: Several lines of evidence point to a relationship between serotonergic dysfunction, negative mood states, and excessive alcohol intake, which may be mediated in part by reduced alcohol‐induced sedation.
Ethanol Decreases Expression of p21 and Increases Hyperphosphorylated pRb in Cell Lines of Squamous Cell Carcinomas of the Head and Neck
Authors: Hager Gudrun , Formanek Michael , Gedlicka Claudia , Knerer Birgit , Kornfehl Johannes 
Published: April 2006

Background: Alcohol increases the risk of cancers of the upper aerodigestive tract, but the biological mechanisms of this ethanol effect are still unclear. We recently reported that ethanol is able to induce in vitro proliferation accompanied by an increased number of cells in the S phase of the cell cycle in squamous cell carcinoma cell lines of the head and neck (SCCHN). In the current study we investigated the influence of ethanol over a limited period of time (96 hr) on cell cycle–regulating proteins involved in G1/S phase transition.Methods: Synchronized cells of SCCHN cell lines JPPA (larynx) and SCC 9 and SCC 25 (tongue), as well as HaCaT (human immortalized keratinocytes)—used as a control—were cultured for 96 hr in the presence or absence of ethanol (10−3M). At several time intervals the expression of cyclin D1 and p21 and the phosphorylation status of the retinoblastoma protein (pRb) were determined by Western or Northern Blot analysis, or both.Results: Ethanol had no influence on the protein expression of cyclin D1. In contrast, a distinct downregulation of p21 at the protein as well as the mRNA level could be detected. Furthermore, as a downstream event, the hyperphosphorylated form of the pRb increased.Conclusions: In the acute alcohol in vitro experiments, the marked downregulation of the important cell cycle inhibitor p21 and the corresponding increase of hyperphosphorylated pRb accelerate the progression of cells from the G1 to the S phase in the cell cycle. The importance of these data and their relevance to in vivo conditions remain speculative, but it could be a critical step in the multistep process of SCCHN carcinogenesis induced by ethanol.