bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropeptide Y Reduces Oral Ethanol Intake in Alcohol‐Preferring (P) Rats Following a Period of Imposed Ethanol Abstinence
Authors: Gilpin Nicholas W. , Stewart Robert B. , Murphy James M. , Li Ting‐Kai , Badia‐Elder Nancy E.
Published: November 2003

Background: Intracerebroventricular infusion of NPY has been shown to reduce ethanol intake in alcohol‐preferring (P) rats in a limited access procedure. The purpose of the present investigation was to extend this finding to a two‐bottle free‐choice continuous access procedure in groups of rats that either did or did not undergo a period of imposed ethanol abstinence and ethanol reinstatement.

Methods: In experiment 1, female P rats were given 6 weeks of continuous access to ethanol (8% w/v) and water. Ethanol was removed for a period of 2 weeks during which the rats were surgically implanted with a cannula into the lateral ventricle. Following the ethanol abstinence period and immediately before ethanol reinstatement, rats received a single infusion of either artificial cerebrospinal fluid or NPY (10 μg). Ethanol and water intake was measured at both 4 hr and 24 hr after infusion, and 24‐hr intake measures were taken daily for 13 postinfusion days. Experiment 2 was run in parallel with experiment 1, with the exception that rats did not undergo a period of imposed ethanol abstinence. Also, food intake was measured 4 and 24 hr after infusion.

Results: Following 2 weeks of imposed ethanol abstinence (experiment 1), NPY suppressed ethanol intake through postinfusion day 2. After uninterrupted continuous access to ethanol (experiment 2), NPY suppressed ethanol intake to a lesser extent and this effect lasted only 24 hr. NPY increased food intake at the 4‐hr but not the 24‐hr measure.

Conclusions: Previous findings that central administration of NPY suppresses ethanol intake in P rats are extended by this study to a continuous access procedure, and the effect is amplified following a period of imposed ethanol abstinence. This effect of NPY compares favorably to results obtained with other treatments tested in similar animal models and provides support for a role of NPY in an allostasis model of addiction.
A Polymorphism in the α4 Nicotinic Receptor Gene (Chrna4) Modulates Enhancement of Nicotinic Receptor Function by Ethanol
Authors: Butt Christopher M. , Hutton Scott R. , Stitzel Jerry A. , Balogh Seth A. , Owens Jeremy C. , Collins Allan C.
Published: November 2003

Background: Several studies indicate that ethanol enhances the activity of α4β2 nicotinic acetylcholine receptors (nAChR). Our laboratory has identified a polymorphism in the α4 gene that results in the substitution of an alanine (A) for threonine (T) at amino acid position 529 in the second intracellular loop of the α4 protein. Mouse strains expressing the A variant have, in general, greater nAChR‐mediated 86Rb+ efflux in response to nicotine than strains with the T variant. However, the possibility of the polymorphism modulating the effects of ethanol on the 86Rb+ efflux response has not been investigated.

Methods: We have used the 86Rb+ efflux method to study the acute effects of ethanol on the function of the α4β2 nAChR in the thalamus in six different mouse strains. Experiments were also performed on tissue samples taken from F2 intercross animals. The F2 animals were derived from A/J mice crossed with a substrain of C57BL/6J mice that carried a null mutation for the gene encoding the β2 nAChR subunit.

Results: In strains carrying the A polymorphism (A/J, AKR/J, C3H/Ibg), coapplication of ethanol (10–100 mM) with nicotine (0.03–300 μM) increased maximal ion flux when compared with nicotine alone with no effect on agonist potency. In contrast, ethanol had little effect on the nicotine concentration‐response curve in tissue prepared from strains carrying the T polymorphism (Balb/Ibg, C57BL/6J, C58/J). Experiments with the F2 hybrids demonstrated that one copy of the A polymorphism was sufficient to produce a significant enhancement of nAChR function by ethanol (50 mM) in animals that were also β2 +/+. Ethanol had no effect on nicotine concentration‐response curves in T/T β2 +/+ animals.

Conclusions: The results suggest that the A/T polymorphism influences the initial sensitivity of the α4β2 nAChR to ethanol.
Serotonin Transporter Gene Variation is Associated with Alcohol Sensitivity in Rhesus Macaques Exposed to Early‐Life Stress
Authors: Barr Christina S. , Newman Timothy K. , Becker Michelle L. , Champoux Maribeth , Lesch Klaus Peter , Suomi Stephen J. , Goldman David , Higley J. Dee
Published: November 2003

Background: Decreased sensitivity to alcohol has been demonstrated to be a predictor of alcoholism in humans, and variation in the gene‐linked polymorphic region of the serotonin transporter (5‐HTTLPR) is associated with the response to the motor‐impairing effects of alcohol. In a nonhuman primate model of excessive alcohol intake, we have shown that decreased serotonin turnover is associated with both lower initial sensitivity to alcohol and higher prospective alcohol consumption using rhesus macaques. In addition, we have demonstrated that macaques separated from their mothers and reared in peer‐only groups are more likely to consume alcohol as adults.

Method: To examine the relationship between serotonin transporter genotype, early rearing experience, and initial sensitivity to alcohol, peer‐ and mother‐reared, adolescent, alcohol‐naive rhesus macaques (n= 123) were rated for intoxication after intravenous administration of ethanol (2.2 g/kg and 2.0 g/kg for males and females, respectively) during two testing periods. Serotonin transporter (rh5‐HTTLPR) genotype was determined using polymerase chain reaction followed by gel electrophoresis, and data were analyzed using ANOVA and the Mann‐Whitney U test.

Results: Our analyses demonstrate an effect of serotonin transporter gene variation on ethanol sensitivity, such that animals homozygous for the l allele exhibited decreased sensitivity to the ataxic and sedating effects of alcohol. This effect remained after correction for blood ethanol concentrations and birth cohort. When animals were segregated according to rearing condition, serotonin transporter gene variation predicted intoxication scores among peer‐reared animals.

Conclusions: As in some human reports, this study demonstrates a diminution in the response to alcohol in animals homozygous for the l rh5‐HTTLPR allele. The phenotypic expression of this genotype in l/s animals, however, is environmentally dependent.
National Survey of Hepatocellular Carcinoma in Heavy Drinkers in Japan
Authors: Horie Yoshinori , Yamagishi Yoshiyuki , Kajihara Mikio , Kato Shinzo , Ishii Hiromasa
Published: November 2003

Background: The major cause of hepatocellular carcinoma (HCC) in the general Japanese population is an infection related to hepatotropic viruses, especially hepatitis virus C (HCV). Even in heavy drinkers, the major cause of HCC is HCV infection. However, HCC without viral infection has been reported in heavy drinkers. Alcohol has been also reported to be associated with an increased risk of cancer. In this study, we investigated aspects of HCC pathogenesis in heavy drinkers in Japan.

Methods: Questionnaires were sent to 1350 hospitals authorized by the Japanese Society of Gastroenterology. The questionnaires asked about the number of inpatients with the different types of alcoholic liver diseases, admitted to each hospital between 1998 and 2001.

Results: The percentage of heavy drinkers among all admitted patients with liver diseases or liver cirrhosis was approximately 15%. Of the patients with alcoholic liver cirrhosis, the cirrhosis was derived from alcohol alone in 61% and from alcohol plus a virus in 39% of patients. Furthermore, the percentage of patients with alcoholic liver cirrhosis caused by alcohol alone and who did not have HCC was 80%. However, the percentage of HCC patients who tested negative for viral hepatitis serum markers was 27% of the total number of heavy drinkers admitted for HCC. A study mainly on liver cirrhosis performed in the early 1990s demonstrated that the alcohol‐alone group accounted for 44% of admitted patients with alcoholic liver cirrhosis and 18% of heavy drinkers admitted for HCC.

Conclusions: Because the consumption of alcohol is increasing in Japan, the frequency and number of cases of alcoholic liver cirrhosis are increasing. Viral hepatitis infection, however, still plays an important role in hepatocarcinogenesis in heavy drinkers. Radiographical examination is recommended even in patients with alcoholic liver cirrhosis who test negative for serum markers of viral hepatitis.
Association Between γ‐Glutamyl Transpeptidase Activity and Status of Disorders Constituting Insulin Resistance Syndrome
Authors: Yokoyama Hirokazu , Moriya Susumu , Homma Yasuhiko , Ogawa Tetsuhei
Published: November 2003

Background:Serum γ‐glutamyl transferase (γGTP) activity is a well‐established marker of alcohol consumption. However, recently, a correlation between serum γGTP activity and insulin resistance status has been demonstrated.

Methods:To determine whether serum γGTP activity could be associated with the status of various disorders caused by increased insulin resistance levels, namely, insulin resistance syndrome, a cross‐sectional study for 11,884 Japanese men was performed. They were divided into three groups by their age, and associations between γGTP and various indexes of insulin resistance syndrome were studied by multiple logistic regression analysis in which subjects' drinking styles were corrected for in each age bracket.

Results:Consuming ethanol more than 40 g/day, body mass index more than 25.9 kg/m2, and triglyceride levels more than 150 mg/dl were significant risk factors accounting for increased γGTP activity (more than 78 IU/liters) irrespective of age. In addition, when subjects of 40 to 59 years old were selectively studied, hypertension, hypercholesteremia, hyperuricemia, and increased glycohemoglobin A1C levels were also significant risk factors for increased γGTP activity.

Conclusions:There are significant associations between γGTP and the status of insulin resistance syndrome. In addition to excessive alcohol consumption, the status of insulin resistance syndrome could affect subjects' γGTP activities.
Correlation Between Insulin Resistance and γ‐Glutamyl Transpeptidase Sensitivity in Light Drinkers
Authors: Moriya Susumu , Yokoyama Hirokazu , Hirose Hiroshi , Ishii Hiromasa , Saito Ikuo
Published: November 2003

Background:Our previous studies suggested that serum γ‐glutamyl transpeptidase (GGTP) level was correlated with insulin resistance level estimated by the homeostasis model assessment in teetotalers and occasional drinkers. In the surveys, strong correlation between GGTP and triglyceride also was observed. This study examined whether the correlation held true for regular drinkers.

Methods:Seven hundred and seventeen male subjects in annual health checkups were divided into three groups according to their drinking styles and further divided into four subgroups according to their serum GGTP levels. In the other surveys, they were ranked by their amount of ethanol consumption. The correlation between GGTP and insulin resistance level was studied in each group.

Results:Single regression analysis and analysis of variance showed that GGTP level was significantly correlated with insulin resistance level as determined by the homeostasis model assessment, as well as with triglyceride level regardless of subjects' drinking styles. The associations were confirmed by multiple regression analyses in which age, levels of uric acid, total cholesterol, high‐density lipoprotein cholesterol, and body mass index were adjusted, at least in nondrinkers or light drinkers. However, the multiple regression analyses indicated that the association between GGTP and insulin resistance level was not significant in subjects who take ethanol more than five times per week. The studies according to the amount of subjects' ethanol consumption indicated that the association between GGTP and insulin resistance was significant in the subjects who take ethanol up to 280 g/week.

Conclusion:Individual variation in insulin resistance status may contribute to individual variations of sensitivity of GGTP to ethanol intake, at least in light drinkers.
Ethanol Induces Transforming Growth Factor‐α Expression in Hepatocytes, Leading to Stimulation of Collagen Synthesis by Hepatic Stellate Cells
Authors: Kato Junji , Sato Yasuhiro , Inui Noriaki , Nakano Yoichiro , Takimoto Rishu , Takada Kohich , Kobune Masayoshi , Kuroiwa Ganji , Miyake Sachie , Kohgo Yutaka , Niitsu Yoshiro
Published: November 2003

Background: Liver fibrosis often develops in alcoholic liver diseases without accompanying inflammation; however, the underlying mechanism is unclear. Using ethanol‐exposed human HepG2 hepatoblastoma cells as a model for alcoholic liver diseases, we previously found that ethanol exposure causes HepG2 cells to secrete a ∼6000 Da nonheparin‐binding polypeptide that stimulates collagen synthesis in human IMR‐90 fibroblasts. The aim of the current study was to characterize and identify this factor.

Methods: Concentration of type I procollagen peptide and transforming growth factor (TGF)‐α was assessed by enzyme‐linked immunosorbent assay. TGF‐α protein expression was examined by Western blot. Type I collagen messenger RNA expression in rat hepatic stellate cells was assessed by reverse transcription‐polymerase chain reaction.

Results: The collagen‐stimulating activity in conditioned media from ethanol‐exposed HepG2 cells to stimulate type I procollagen peptide synthesis of IMR‐90 cells was specifically inhibited by addition of anti‐TGF‐α antibodies. Western blot analysis showed increased TGF‐α protein expression in ethanol‐treated HepG2 cells. TGF‐α in conditioned medium from ethanol‐exposed HepG2 cells stimulated type‐I collagen messenger RNA expression in rat hepatic stellate cells.

Conclusions: These results suggest that TGF‐α derived from ethanol‐exposed hepatocytes may contribute to the development of hepatic fibrosis in alcoholic liver diseases.
Association Analyses Between Polymorphisms of the Phase II Detoxification Enzymes (GSTM1, NQO1, NQO2) and Alcohol Withdrawal Symptoms
Authors: Okubo Takehito , Harada Shoji , Higuchi Susumu , Matsushita Sachio
Published: November 2003

Background: NRH‐quinone oxidoreductase 2 (NQO2) along with glutathione S‐transferase M1 (GSTM1) and NAD(P)H‐quinone oxidoreductase 1 (NQO1), which is involved in phase II detoxification reactions, is thought to be important for detoxification of catechol o‐quinones in the central nervous system. Our previous study revealed that the human NQO2 gene is highly polymorphic. In this study, we investigated a possible association between polymorphisms of the GSTM1, NQO1, and NQO2 genes and alcohol withdrawal symptoms such as delirium tremens, hallucination, and seizure.

Methods: A total of 247 Japanese male alcoholic patients with alcohol withdrawal symptoms or without the symptoms, and 134 age‐matched Japanese male controls (nonhabitual drinkers), were examined by using polymerase chain reaction (PCR), PCR restriction fragment length polymorphism, PCR‐based single‐strand conformational change polymorphism, and PCR direct sequencing analyses.

Results: A significant difference was found between alcoholic patients and controls in genotype frequency at an insertion/deletion site in the promoter region of the NQO2 gene (p= 0.0014). The frequency of the homozygous genotype for the D allele at this locus was significantly higher in delirium tremens‐positive patients (p= 0.0004) and in hallucination‐positive patients (p= 0.0001), and in patients displaying both delirium tremens and hallucination (p= 0.0002), than in controls. The values were still significant after Bonferroni correction. On the other hand, no significant difference was detected for allele frequencies or genotype frequencies for the other polymorphic loci of the NQO2 gene. Moreover, GSTM1 gene deletion and missense mutation (Pro187Ser) of the NQO1 gene showed no significant association with alcohol withdrawal symptoms.

Conclusion: Present data suggest that an insertion/deletion polymorphism in the promoter region of the NQO2 gene plays an important role in the pathogenesis of alcoholism and alcohol withdrawal symptoms.
In Vivo Study of Salsolinol Produced by a High Concentration of Acetaldehyde in the Striatum and Nucleus Accumbens of Free‐Moving Rats
Authors: Jamal Mostofa , Ameno Kiyoshi , Ameno Setsuko , Okada Naoko , Ijiri Iwao
Published: November 2003

Background:Salsolinol, a neuropharmacologically active compound, is formed by the condensation of acetaldehyde (AcH) with dopamine (DA) in the brain. The aim of our study was to examine the effect of a high concentration of AcH on salsolinol formation and to compare the release of DA, serotonin (5‐HT), and salsolinol in the striatum and nucleus accumbens (NAc) in free‐moving rats.

Methods:After the insertion of a microdialysis probe, male Wistar rats (250–300 g) were treated with cyanamide (CY, a potent aldehyde dehydrogenase inhibitor) + ethanol (EtOH), CY + 4‐methylpyrazole (4‐MP, a strong alcohol dehydrogenase inhibitor) + EtOH, 4‐MP + EtOH, CY, and 4‐MP. Simultaneous quantitation of DA, 5‐HT, and salsolinol in dialysates was performed by using in vivo microdialysis coupled with high‐performance liquid chromatography with an electrochemical detector and blood EtOH and AcH by using a head‐space gas chromatographic method.

Results:Salsolinol was detected only in the CY + EtOH groups in both the striatum and NAc, and we also detected a high AcH concentration in the blood in those groups. A correlation was found between the dialysate levels of salsolinol and blood concentrations of AcH. The striatal levels of DA and 5‐HT were approximately two times higher, whereas salsolinol levels were approximately three times higher compared with the usual level in the NAc. No significant difference of DA and 5‐HT levels in the dialysates was observed in either the control or the other study groups.

Conclusion:Our observation suggested that the brain salsolinol formation may depend on the concentrations of DA and AcH in freely moving rats, and there is no effect of a high concentration of AcH on DA and 5‐HT levels in the striatum and NAc.
Influence of Acute Alcohol Load on Metabolism of Skeletal Muscles—Expired Gas Analysis During Exercise
Authors: Shiraishi Koichi , Watanabe Mitsuyuki , Motegi Shigeyuki , Nagaoka Reiko , Matsuzaki Shohei , Ikemoto Hiroki
Published: November 2003

Background: The chronic intake of alcohol affects the function of skeletal muscles. To elucidate the influence of acute alcoholic load on muscular metabolism during exercise, we analyzed expired gases to measure the volume of consumed oxygen and the volume of exhaled CO2.

Methods: Healthy volunteers were enrolled for the study. For the exercise test, they were asked to rest for 5 min, warm up on an aerobike at 20 W for 2 min, and then gradually increase the load by 2 W every 6 sec. On another day, they were asked to drink 0.5 to 0.6 g/kg ethanol in 30 min, rest for 30 min, and then do the test. The expired gas analysis was used to measure changes in the anaerobic threshold and the respiratory compensation point. The blood concentrations of lactate, ethanol, and acetate also were measured.

Results: The anaerobic threshold showed no significant change in the case of exercise without alcoholic load. The respiratory compensation point decreased significantly in the case of alcoholic load (p < 0.001), and the interval from the anaerobic threshold to the respiratory compensation point decreased (p < 0.02). The blood concentration of lactate increased, after alcoholic load, to a level significantly higher than the level measured before the alcoholic load (p < 0.001). It showed a marked increase immediately after exercise stress (p < 0.001). The blood concentration of acetate tended to decrease after exercise load, but no significant change was noted.

Conclusions: The anaerobic threshold, which is the limit of the aerobic glycolytic system (i.e., the so‐called aerobic exercise limit) was not influenced by exercise under an acute alcoholic load. However, after the production of lactate started, the respiratory compensation point, which is the limit of the metabolic compensatory action, appeared earlier. This suggested that the intake of alcohol would influence the energy metabolism of skeletal muscles by a mechanism in which the disturbed metabolism of lactate in skeletal muscles was mainly involved.
Effects of Fusel Oil on Animal Hangover Models
Authors: Hori Hisako , Fujii Wataru , Hatanaka Yutaka , Suwa Yoshihide
Published: November 2003

Background: Fusel oil has been reported to have undesirable side effects such as hangover. However, the relationship between fusel oil and hangover has been investigated insufficiently. In this study, we investigated the effects of fusel oil and their ingredients contained in alcoholic beverages by using animal hangover models.

Methods: Ethanol and fusel oil were simultaneously administered to Suncus murinus, and emetic responses were observed for 60 min. Ethanol and fusel oil were simultaneously administered to mice immediately after intake of saccharin solution; on the next day, the mouse's saccharin solution intake was measured.

Results: The volatile fraction (fusel oil) of whisky had no remarkable effect on ethanol‐induced emetic responses in suncus. Whisky had the most suppressive effect on ethanol‐induced conditioned taste aversion in mice among the various alcoholic beverages tested. The volatile fraction (fusel oil) of whisky suppressed the ethanol‐induced conditioned taste aversion. In contrast, the nonvolatile fraction of whisky had no effect. The administration of isoamyl alcohol (5 mg/kg) and isoamyl acetate (10 and 40 μg/kg), ingredients of fusel oil, significantly suppressed the ethanol‐induced conditioned taste aversion.

Conclusions: The fusel oil in whisky had no effect on the ethanol‐induced emetic response, but it suppressed taste‐aversion behavior in animal models of hangover symptoms. These results suggest that the fusel oil in whisky alleviates hangover, contrary to the common belief.
A Culturally Responsive, Family‐Enhanced Intervention Model
Authors: Boyd‐Ball Alison J.
Published: November 2003

The Multicultural Interventions for Adolescent Substance Use, referred to as The Shadow Project, was a 3‐year, NIAAA‐funded pilot study involving 60 American Indian families who had a youth entering alcohol and drug inpatient treatment. Participation was voluntary and involved comparison of two different treatment modalities: treatment as usual and a brief family‐enhanced intervention. In adapting this family‐based intervention specifically for American Indian families, a cultural approach to assessment and intervention was integrated into the process, with the intervention focusing on building support around the youth to attain abstinence and assuring the youth that their family, community, and substance abuse counselor were motivating influences. Five areas were assessed in the family observation tasks: relationship building, positive reinforcement, limit setting, monitoring, problem solving, and communication. Cultural adaptation was made for two of the five tasks. Two legends were used to assess the families' skill level in relationship building, problem solving, and communication as a family unit. By incorporating Indian stories, families were encouraged to respond in a culturally appropriate manner. Preliminary findings show that these stories were linked to child prosocial behavior and the percentage of days abstinent from individual drug use. This pilot project also adapted culturally responsive instruments, tasks, and validity to this population. The first year required adaptation of recruitment methods, tribal and treatment center agreements, referral contacts, and implementation of intervention and follow‐up with adolescents and their families. The second year was composed of intervention implementation and follow‐up assessments. To determine the intervention program's long‐term effect on reducing adolescent alcohol and other drug use, all families were followed up and assessed 11 months after they left treatment. The third and final year of the study included follow‐up, data entry, and data analysis.
Alcohol‐Related Health Disparities and Treatment‐Related Epidemiological Findings Among Whites, Blacks, and Hispanics in the United States
Authors: Caetano Raul
Published: November 2003

This article briefly reviews the alcohol epidemiological evidence on health disparities across whites, blacks, and Hispanics. Compared with whites, Hispanic men have higher rates of alcohol‐related problems, intimate partner violence, and cirrhosis mortality; black men have higher rates of intimate partner violence and cirrhosis mortality. All groups see treatment as an appropriate intervention to address alcohol problems, and there also is support for prevention.
Human Neural Stem Cells Are More Sensitive Than Astrocytes to Ethanol Exposure
Authors: Hao Hsiao‐Nan , Parker Graham C. , Zhao Jane , Barami Kaveh , Lyman William D.
Published: November 2003

Background: Exposure to ethanol (EtOH) can be deleterious to the developing central nervous system. The mechanisms by which EtOH exposure induces neural pathology in utero remain unclear. However, EtOH‐induced increases in protein kinase C (PKC) have been associated with apoptosis in human primary cell cultures. Although the toxic effects of EtOH on differentiated neural cells have been studied in laboratory animal models, the susceptibility of the human neural stem cells (NSCs) that predominate in the central nervous system during embryonic development has not been addressed.

Methods: For this study, fetal human brain cells, which satisfied the criteria for NSCs by being CD133‐positive, nestin‐positive, and differentiated glial fibrillary acidic protein‐positive human astrocytes, were studied. The cytotoxic potential of EtOH in NSC and astrocyte cultures was studied by using morphological and biochemical methods. In addition, membrane and cytosolic fraction PKC activity for each cell type was assessed.

Results: NSC showed a dose‐dependent increase in EtOH‐induced toxicity as estimated by terminal transferase‐mediated dUTP nick end labeling (TUNEL) stain and viability assays. TUNEL staining indicating DNA degradation consistent with programmed (apoptotic) cell death was detectable in 90% of NSC 16 hr after 2 hr exposure to 10 mM EtOH. NSC also showed a concentration‐dependent increase in membrane, but not cytosol, PKC activity over the same EtOH dose range. By contrast, astrocytes showed no cytotoxic effects at any concentrations of EtOH used (0–10 mM). PKC activity of both the membrane and cytosolic fragments from astrocytes also was unaffected by this range of doses.

Conclusions: This study demonstrates the susceptibility of human NSCs, compared with astrocytes, to EtOH and indicates that alterations in PKC signal transduction in NSC may play a role in EtOH‐induced neuropathological processes.
Project Match Treatment Participation and Outcome by Self‐Reported Ethnicity
Authors: Tonigan J. Scott
Published: November 2003

Background: There is a lively ongoing debate concerning the need for culturally congruent alcohol treatment, with the assumption that such treatment would meaningfully address treatment outcome disparities among ethnic minorities. Although valid on the face of it, no randomized clinical trials have yet prospectively investigated and documented whether, in fact, different ethnic groups actually fare better or worse from one another when offered mainstream, culturally “incongruent” treatment. The purpose of this study was to contrast Hispanic, black, and white client treatment engagement and outcome in an effort to identify potential health disparities related to client ethnicity.

Methods: The Project Match outpatient (N= 952) and aftercare (N= 774) samples were divided according to self‐reported ethnicity: Hispanic (n= 141; 8%), black (n= 168; 10%), and white (n= 1380; 80%). Controlling for socioeconomic status using the Hollingshead Occupational scale, the three ethnic groups were contrasted on pretreatment characteristics, rates of treatment attendance, three scales of therapeutic alliance, satisfaction with treatment, and drinking outcomes for the 12 months after treatment.

Results: Ethnic differences in rates of therapy attendance were not robust and dissipated after controlling for socioeconomic status. No mean ethnic differences in ratings of therapeutic bonding and agreement with therapy goals were obtained, but blacks and Hispanics reported higher agreement on the value of therapeutic tasks relative to whites. Nevertheless, whites reported significantly higher global satisfaction with treatment relative to Hispanics and blacks. No ethnic main effect was found in drinking intensity during the 12‐month follow‐up. In contrast and only in the outpatient sample, blacks (n= 51) reported significantly higher rates of monthly abstinence relative to whites (n= 679).

Conclusions: Pretreatment characteristics predictive of positive treatment outcome favored white clients relative to Hispanic and black clients, but Hispanic and black clients fared at least as well as white clients during the 12‐month follow‐up, at least on two measures of drinking behavior. The absence, then, of poorer drinking outcomes for the ethnic minorities suggests that they may mobilize (1) different behavior change strategies and/or (2) additional social resources to achieve comparable drinking outcomes with white clients. Specific recommendations for future research are made.
Effects of Acute Social Stress on Alcohol Consumption in Healthy Subjects
Authors: de Wit Harriet , Söderpalm Anna H. V. , Nikolayev Lilia , Young Elizabeth
Published: November 2003

Background: There has been renewed interest in interactions between stress and use of drugs and alcohol. Although there is evidence that stress increases drug use in human drug users and in laboratory animals, the processes by which stress affects drug‐motivated behavior are not understood. Here we examined the effects of an acute social stressor (performing a mental arithmetic task in front of an audience) on consumption of ethanol or placebo beverages in healthy social drinkers.

Methods: Thirty‐seven men and women, ages 21–35, were randomly assigned to a placebo (n= 15) or ethanol group (n= 22). Subjects participated in two sessions, one with stress (Trier Social Stress Test) the other without stress. In each session, immediately after the stress or no‐stress period, subjects consumed the first dose (placebo or 0.3 g/kg of ethanol for men or 0.2 g/kg for women). Then, subjects were allowed to choose up to six more beverages (0.1 g/kg each for the ethanol group or placebo beverages for the placebo group). Measures included percentage of beverage consumed, salivary cortisol level, heart rate, blood pressure, and subjective ratings of mood and drug effect.

Results: Subjects in both the placebo and ethanol groups consumed significantly more of their beverages after stress, compared to no stress. Stress increased anxiety, uneasiness, and produced some stimulant‐like effects and, in the ethanol group, it dampened some of the acute subjective effects of ethanol. The direct physiologic and mood effects of the stress were fairly short‐lived.

Conclusions: It is concluded that acute stress may produce a modest increase in alcohol consumption in healthy, nonproblem social drinkers but that this increase is not directly related to the pharmacological effects of the drug. Nonpharmacological factors may include expectancies, thirst, or nonspecific facilitation of ongoing behaviors.
Development and Initial Validation of the Hangover Symptoms Scale: Prevalence and Correlates of Hangover Symptoms in College Students
Authors: Slutske Wendy S. , Piasecki Thomas M. , Hunt‐Carter Erin E.
Published: November 2003

Background: Despite its ubiquity, hangover has received remarkably little systematic attention in alcohol research. This may be due in part to the lack of a standard measure of hangover symptoms that cleanly taps the physiologic and subjective effects commonly experienced the morning after drinking. In the present study, we developed and evaluated a new scale, the Hangover Symptoms Scale (HSS), to potentially fill this void.

Methods: Participants were 1230 currently drinking college students (62% women, 91% Caucasian). They were administered a self‐report inventory in which they reported the frequency of occurrence of 13 different hangover symptoms during the past 12 months. Participants also reported their history of alcohol involvement, alcohol‐related problems, and family history of alcohol‐related problems.

Results: On average, participants experienced 5 out of 13 different hangover symptoms in the past year; the three most common symptoms were feeling extremely thirsty/dehydrated, feeling more tired than usual, and headache. Higher scores on the HSS were significantly positively associated with the frequency of drinking and getting drunk and the typical quantity of alcohol consumed when drinking, a personal history of alcohol‐related problems, and a family history of alcohol‐related problems. After controlling for sex differences in alcohol involvement, women had higher scores on the HSS than men.

Conclusions: The HSS appears to capture a reasonably valid set of adjectives describing common hangover effects. It is hoped that the availability of a brief, valid hangover assessment such as the HSS will encourage further study of hangover's frequency, correlates, and consequences. Future research is needed to explore the performance of a re‐worded HSS in laboratory settings, which may help bridge the gap between laboratory and survey investigations of hangover.
Cardiovascular Responses to Physical and Psychological Stress in Female Alcoholics With Transitory Hypertension After Early Abstinence
Authors: Bernardy Nancy C. , King Andrea C. , Lovallo William R.
Published: November 2003

Background: Male alcoholic patients with acute withdrawal hypertension have shown exaggerated cardiovascular reactivity to stress after 3 to 4 weeks of abstinence, although resting blood pressures (BP) had returned to normal. Studies of this nature, however, have not been extended to women.

Methods: In this study, 32 alcohol‐dependent women, abstinent for 4 weeks, were compared with 16 healthy controls on cardiovascular hemodynamics during rest and in response to 2 moderately aversive stressors: isometric handgrip and a speech task. The alcoholics were placed according to withdrawal BP into transitory hypertensive (tHT; n= 16; BP ≥140/90 mm Hg) and normotensive (NT; n= 16; BP <140/90 mm Hg) subgroups.

Results: During stress testing, the transitory hypertensive women had increased diastolic BP (p < 0.01), a higher peripheral resistance index (p < 0.05), and a reduced cardiac efficiency index (p < 0.03) relative to the normotensive and control subjects.

Conclusions: This cardiovascular pattern suggests that both cardiac and vascular functions were altered adversely in the transitory hypertensives. In contrast to men examined in previous studies, the transitory hypertensive women had no exaggeration of BP reactivity, but instead showed sustained alterations of resting cardiovascular function in relation to chronic alcohol consumption. Although the pattern of cardiovascular dysregulation seems to be different in female alcoholics than in males, it is consistent with studies showing that cardiovascular effects in women are more severe than in men and emerge at a lower threshold level of chronic drinking.
Effect of Ethanol on Visual‐Vestibular Interactions During Vertical Linear Body Acceleration
Authors: Schmäl Frank , Thiede Oliver , Stoll Wolfgang
Published: November 2003

Background: Ethanol led to disturbed dynamic visual acuity (DVA) during vertical linear acceleration (VLA; amplitude, 5 cm; frequency, 1.2 Hz). The aim of this study was to analyze whether suppression of visual‐oculomotor or vestibular pathway is responsible for the disturbance of DVA.

Methods: Twenty volunteers were investigated before and after ethanol consumption (mean breath alcohol concentration, 0.32 mg/liter). Vertical eye movements and linear head acceleration were recorded. Tested stimuli were vestibular (VLA in the dark), visual (smooth pursuit), and combined (VLA plus fixation on an earth‐fixed target) stimulation; visual suppression (VLA plus fixation of a head‐fixed target); static visual acuity; and DVA. Parameters of analysis were gain, sensitivity, eye velocity and amplitude, latency between onset of head acceleration and start of eye movement, correct and wrong answers during static visual acuity and DVA testing, feeling of drunkenness (FOD), and breath alcohol concentration.

Results: Both during isolated visual and during combined visual‐vestibular stimulation, alcohol induced a significant latency increase. Furthermore, DVA was disturbed after ethanol consumption. Test subjects with a strong alcohol‐induced disturbance of DVA presented during isolated visual stimulation a significantly higher latency change than volunteers with a minor alcohol‐induced disturbance of DVA. On the basis of the FOD, two groups were formed (one with a slight and one with a strong FOD). The two groups differed significantly concerning the alcohol‐induced latency increase during isolated visual stimulation and the alcohol‐induced disturbance of DVA.

Conclusions: Ethanol leads to a disturbance of the visual‐oculomotor system and, thus, even during combined visual‐vestibular stimulation, to a latency increase. This “delay” is responsible for the disturbance of DVA. This alcohol‐induced suppression of the visual‐oculomotor system and the disturbance of DVA show a significantly positive correlation with the subjective FOD.
Evaluation of Aldehyde Dehydrogenase 1 Promoter Polymorphisms Identified in Human Populations
Authors: Spence John P. , Liang Tiebing , Eriksson C.J. Peter , Taylor Robert E. , Wall Tamara L. , Ehlers Cindy L. , Carr Lucinda G.
Published: November 2003

Background: Cytosolic aldehyde dehydrogenase, or ALDH1A1, functions in ethanol detoxification, metabolism of neurotransmitters, and synthesis of retinoic acid. Because the promoter region of a gene can influence gene expression, the ALDH1A1 promoter regions were studied to identify polymorphism, to assess their functional significance, and to determine whether they were associated with a risk for developing alcoholism.

Methods: Sequence analysis was performed in the promoter region by using Asian, Caucasian, and African American subjects. The resulting polymorphisms were assessed for frequency in Asian, Caucasian, Jewish, and African American populations and tested for associations with alcohol dependence in Asian and African American populations of alcoholics and controls. The functional significance of each polymorphism was determined through in vitro expression analysis by using HeLa and HepG2 cells.

Results: Two polymorphisms, a 17 base pair (bp) deletion (−416/−432) and a 3 bp insertion (−524), were discovered in the ALDH1A1 promoter region:ALDH1A1*2 and ALDH1A1*3, respectively. ALDH1A1*2 was observed at frequencies of 0.035, 0.023, 0.023, and 0.012 in the Asian, Caucasian, Jewish, and African American populations, respectively. ALDH1A1*3 was observed only in the African American population, at a frequency of 0.029. By using HeLa and HepG2 cells for in vitro expression, the activity of the luciferase reporter gene was significantly decreased after transient transfection of ALDH1A1*3‐luciferase compared with the wild‐type construct ALDH1A1*1‐luciferase. In an African American population, a trend for higher frequencies of the ALDH1A1*2 and ALDH1A1*3 alleles was observed in a population of alcoholics (p= 0.03 and f= 0.12, respectively) compared with the control population.

Conclusions: ALDH1A1*2 and ALDH1A1*3 may influence ALDH1A1 gene expression. Both ALDH1A1*2 and ALDH1A1*3 produce a trend in an African American population that may be indicative of an association with alcoholism; however, more samples are required to validate this observation. The underlying mechanisms contributing to these trends are still unknown.
Increased Salivary Cortisol Concentrations During Chronic Alcohol Intoxication in a Naturalistic Clinical Sample of Men
Authors: Adinoff Bryon , Ruether Keith , Krebaum Steven , Iranmanesh Ali , Williams Mark J.
Published: November 2003

Background: Cortisol, the primary glucocorticoid in humans, is intimately involved in the regulation of such varied and critical biological processes as emotion, cognition, reward, immune functioning, and energy utilization. A persistent increase in cortisol concentration as a result of chronic intoxication could therefore result in alcohol‐related disorders such as sleep disruption, cognitive deficits, diabetes, and mood disturbances. Although moderate levels of acute alcohol ingestion are reported to produce an increase in cortisol levels, it is uncertain whether cortisol remains persistently increased during long‐term chronic intoxication.

Methods: Salivary cortisol and breath alcohol concentrations (BAC) were obtained on 73 subjects with primary alcohol dependence on initial presentation for treatment and 22 alcohol‐dependent subjects participating in a residential treatment program.

Results: Both intoxicated alcohol‐dependent subjects (n= 38) and nonintoxicated subjects in acute alcohol withdrawal (n= 30) demonstrated significantly increased salivary cortisol concentrations compared with abstinent subjects (n= 27; p < 0.001). Nonintoxicated subjects in acute withdrawal demonstrated significantly increased salivary cortisol concentrations compared with highly intoxicated subjects (BAC >100 mg/dl) but were similar to subjects with lower levels of intoxication (BAC, 10–100 mg/dl).

Conclusions: Chronic alcohol‐dependent subjects experience continuously increased concentrations of cortisol during both intoxication and withdrawal. Increased levels of cortisol during chronic intoxication seem to progressively increase with the onset of withdrawal. This suggests a daily cycle of hypercortisolemia during the active drinking phase, with further increases on the cessation of drinking and the emergence of withdrawal symptoms. Persistently increased levels of cortisol may extract a costly allostatic load, resulting in significant central nervous system and peripheral organ morbidity.
Binding of Acetaldehyde to a Glutathione Metabolite: Mass Spectrometric Characterization of an Acetaldehyde‐Cysteinylglycine Conjugate
Authors: Anni Helen , Pristatsky Pavlo , Israel Yedy
Published: November 2003

Background: Ethanol administration decreases hepatic glutathione levels and increases urinary sulfhydryl excretion. Ethanol‐induced liver injury is blunted by the administration of glutathione precursors. Acetaldehyde generated in the metabolism of ethanol binds to a number of amino acid residues in proteins and peptides, but it does not react readily with glutathione. Due to the possible role of acetaldehyde in cysteine and glutathione homeostasis, we investigated the reaction of acetaldehyde to cysteinylglycine, the dipeptide generated in vivo in the hydrolysis of glutathione by γ‐glutamyltransferase.

Methods: A conjugate between acetaldehyde and cysteinylglycine was generated under physiologically relevant conditions, both in vitro and in vivo. It was separated by a new reverse‐phase high‐performance liquid chromatography method and identified by electrospray ionization/ion trap tandem mass spectrometric analysis.

Results: The conjugate with a stoichiometry of 1:1 between cysteinylglycine and acetaldehyde is most rapidly generated in vitro and was identified by mass spectroscopy as 2‐methyl‐thiazolidine‐4‐carbonyl‐glycine. This thiazolidine derivative is stable in vitro and in biological fluids of rats. The conjugate was present in high concentrations in the bile of rats pretreated with ethanol and an inhibitor of aldehyde dehydrogenase.

Conclusions: The sequestering of cysteinylglycine by acetaldehyde occurs rapidly under physiologic conditions. Long‐lived sulfur‐containing biomolecules that incorporate acetaldehyde might affect cysteine and glutathione homeostasis and may also play a protective role by reducing circulating acetaldehyde levels. The acetaldehyde conjugate or its metabolic products could potentially serve as markers of ethanol consumption.
Treatment of Alcohol Abuse: An Evidence‐Based Review
Authors: Berglund Mats , Thelander Sten , Salaspuro Mikko , Franck Johan , Andréasson Sven , Öjehagen Agneta
Published: November 2003

This article represents the proceedings of a symposium at the 2002 annual meeting of the Research Society on Alcoholism in San Francisco, CA, organized and cochaired by Mats Berglund and Sten Thelander. The presentations were (1) Preventive interventions against hazardous consumption of alcohol, by Mikko Salaspuro; (2) Treatment of alcohol withdrawal, by Johan Franck; (3) Psychosocial treatment for alcohol problems, by Sven Andréasson and Agneta Öjehagen; and (4) Pharmacological treatment of alcohol dependence, by Mats Berglund.
Reverse Selection for Differential Response to the Locomotor Stimulant Effects of Ethanol Provides Evidence for Pleiotropic Genetic Influence on Locomotor Response to Other Drugs of Abuse
Authors: Bergstrom Hadley C. , Palmer Abraham A. , Wood Robin D. , Burkhart‐Kasch Sue , McKinnon Carrie S. , Phillips Tamara J.
Published: November 2003

Background: Addictive drugs share the ability to induce euphoria, which may be associated with their potential for abuse. Replicate mouse lines with high (FAST‐1, FAST‐2) and low (SLOW‐1, SLOW‐2) sensitivity to ethanol‐induced psychomotor stimulation (a possible animal model for the euphoria experienced by humans) have provided evidence for common genetic influences (pleiotropy) on sensitivity to the effects of ethanol and of GABA‐A receptor acting compounds on locomotor activity. Differences between FAST and SLOW mice in locomotor response to certain other drugs were found later in selection. Reverse selection produced lines (r‐FAST‐1, r‐FAST‐2, r‐SLOW‐1, r‐SLOW‐2) with similar locomotor responses to ethanol. These lines are well suited for asking whether the same alleles that influence sensitivity to ethanol are also responsible for these later arising differences in drug sensitivity.

Methods: Two replicate sets of forward‐ and reverse‐selected FAST and SLOW lines were tested for the effects of multiple doses of morphine, cocaine, methamphetamine, nicotine, and scopolamine on their locomotor behavior. We predicted that differences in drug sensitivity between the FAST and SLOW lines would be reduced or eliminated in the reverse‐selected lines.

Results: Differences in sensitivity to morphine, cocaine, methamphetamine, and nicotine that arose in earlier generations of the FAST‐1 and SLOW‐1 lines ultimately also appeared in the FAST‐2 and SLOW‐2 lines. However, some differences between the FAST‐2 and SLOW‐2 lines (those in response to cocaine and methamphetamine) were not seen until several generations after selection had been relaxed. In lines reverse‐selected for sensitivity to ethanol, differences in sensitivity to the other drugs were decreased, eliminated, or even reversed. No differences in scopolamine response were found in the replicate 1 forward‐ or reverse‐selected lines. However, a small difference in scopolamine response in the replicate 2 lines was reversed.

Conclusions: Genes that influence the locomotor response to ethanol also influence locomotor response to other drugs with stimulant effects in the FAST and SLOW mice. The current data most strongly support this conclusion for sensitivity to morphine and nicotine.