bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coregulation of Ethanol Discrimination by the Nucleus Accumbens and Amygdala
Authors: Besheer Joyce , Cox Amy A. , Hodge Clyde W. 
Published: November 2003

Background: Activation of GABAA receptors in the amygdala or nucleus accumbens produces discriminative stimulus effects that substitute fully for those of systemically administered ethanol. This study was conducted to determine if GABAA receptors in the amygdala and nucleus accumbens interactively modulate ethanol discrimination.Methods: Male Long‐Evans rats were trained to discriminate between intraperitoneal injections of ethanol (1 g/kg) and saline on a 2‐lever drug discrimination task. The rats were then surgically implanted with bilateral injection cannulae aimed at the nucleus accumbens and the amygdala.Results: Infusion of the GABAA agonist muscimol in the nucleus accumbens resulted in full substitution for systemically administered ethanol. Concurrent infusion of the GABAA antagonist bicuculline in the amygdala shifted the muscimol substitution curve in the nucleus accumbens 10‐fold to the right.Conclusions: These results indicate that blockade of GABAA receptors in the amygdala significantly reduces the potency of the GABAA agonist in the nucleus accumbens. This suggests that the ethanol‐like stimulus effects of GABAA receptor activation in the nucleus accumbens are modulated by GABAA receptor activity in the amygdala. These data support the hypothesis that the addictive stimulus properties of alcohol are mediated by GABAergic transmission in a neural circuit involving the amygdala and nucleus accumbens.
EEG Low‐Voltage Alpha and Alpha Power in African American Young Adults: Relation to Family History of Alcoholism
Authors: Ehlers Cindy L. , Phillips Evelyn 
Published: November 2003

Background: Several studies support an association between having a low‐voltage EEG and alcohol dependence; however, it is not clear whether this measure represents a risk marker or is a result of years of heavy drinking. The present study's aims were to investigate the prevalence of low‐voltage alpha EEG variants in African American young adults who have not yet developed alcohol dependence and to test for associations between low‐voltage alpha (LVA) EEG, alpha power, and a family history of alcohol dependence.Methods: Clinical ratings and spectral characteristics of the EEG, collected using bipolar recordings, were investigated in 81 African American young adult men and women (18–25 years old) who had no personal history of alcohol dependence. Information on psychiatric diagnoses, personality features, personal drinking and drug use history, and family history (FH) of alcoholism was obtained.Results: Thirty‐two percent (n= 26) of the participants had an LVA EEG variant, and an additional 22% (n= 18) had borderline LVA. The presence of an LVA variant was not associated with drinking status, a family history of alcoholism, or a personal history of anxiety disorders but was associated with significantly higher extroversion scores. Participants who had an FH of alcoholism had significantly higher spectral power in the slow alpha frequencies (7.5–9 Hz). FH was not associated with any significant differences in any other EEG frequency band.Conclusions: These findings suggest that considerable ethic variation may exist in the prevalence of LVA EEG variants. In addition, like findings in other populations of non‐African descent, having an FH of alcohol dependence may be associated with significantly higher voltage in the alpha frequency ranges.
Ethanol Potentiation of Glycine Receptors Expressed in Xenopus Oocytes Antagonized by Increased Atmospheric Pressure
Authors: Davies Daryl L. , Trudell James R. , Mihic S. John , Crawford Daniel K. , Alkana Ronald L. 
Published: November 2003

Background: Behavioral and biochemical studies indicate that exposure to 12 times normal atmospheric pressure (12 ATA) of helium‐oxygen gas (heliox) is a direct, selective ethanol antagonist. The current study begins to test the hypothesis that ethanol acts by a common mechanism on ligand‐gated ion channels by expanding previous hyperbaric investigations on γ‐aminobutyric acid type A (GABAA) receptors (GABAARs) at the biochemical level to α1glycine (GlyRs) expressed in Xenopus oocytes.Methods: Oocytes expressing wild‐type α1 homomeric GlyRs were voltage‐clamped (−70 mV) and tested in the presence of glycine (EC2) ± ethanol (50–200 mM) under 1 ATA control and 3 to 12 ATA heliox conditions. Glycine concentration response curves, strychnine/glycine interactions, and zinc (Zn2+) modulation of GlyR function was also tested.Results: Pressure reversibly antagonized the action of ethanol. The degree of antagonism increased as pressure increased. Pressure did not significantly alter the effects of glycine, strychnine, or Zn2+, indicating that ethanol antagonism by pressure cannot be attributed to alterations by pressure of normal GlyR function. The antagonism did not reflect tolerance to ethanol, receptor desensitization, or receptor rundown.Conclusion: This is the first use of hyperbarics to investigate the mechanism of action of ethanol in recombinant receptors. The findings indicate that pressure directly and selectively antagonizes ethanol potentiation of α1GlyR function in a reversible and concentration‐ and pressure‐dependent manner. The sensitivity of ethanol potentiation of GlyR function to pressure antagonism indicates that ethanol acts by a common, pressure‐antagonism–sensitive mechanism in GlyRs and GABAARs. The findings also support the hypothesis that ethanol potentiation of GlyR function plays a role in mediating the sedative‐hypnotic effects of ethanol.
Subjective Intoxication in Response to Alcohol Challenge: Heritability and Covariation With Personality, Breath Alcohol Level, and Drinking History
Authors: Viken Richard J. , Rose Richard J. , Morzorati Sandra L. , Christian Joe C. , Li Ting‐Kai 
Published: November 2003

Background: Numerous studies have identified differences in subjective response to alcohol in subjects differentiated by family history of alcoholism. Results suggest that genetic influences on individual variation in subjective response to alcohol may be a mechanism for genetic effects on alcohol problems. However, direct evidence for genetic effects on subjective response to alcohol is very limited.Methods: In a sample of 99 adult twin pairs, we studied genetic influences on subjective intoxication after alcohol challenge. The twins ingested a standard dose of ethanol (0.70 g/kg for men/0.65 g/kg for women), and two measures of subjective response to alcohol were assessed.Results: Genetic effects on variation in subjective intoxication reported 1 hr after drinking were significant and substantial: heritability was 0.60 for a 22‐item scale and 0.48 for a brief 2‐item measure. Self‐report measures of neuroticism, psychasthenia, hostility, and family problems shared significant genetic covariation with subjective intoxication. Achieved breath alcohol level, rate of change in breath alcohol on the descending limb, and individual drinking history all shared familial variation with subjective intoxication. No significant genetic effects for subjective intoxication were found 2 hr after drinking, but familial influences remained present, and many of the same personality, drinking history, and breath alcohol variables were predictive of intoxication.Conclusions: Subjective response to alcohol is heritable, and genetic effects on subjective intoxication are partly shared with genetic effects on personality.
The Reliability and Validity of the Self‐Reported Drinking Measures in the Army's Health Risk Appraisal Survey
Authors: Bell Nicole S. , Williams Jeffrey O. , Senier Laura , Strowman Shelley R. , Amoroso Paul J. 
Published: November 2003

Background: The reliability and validity of self‐reported drinking behaviors from the Army Health Risk Appraisal (HRA) survey are unknown.Methods: We compared demographics and health experiences of those who completed the HRA with those who did not (1991–1998). We also evaluated the reliability and validity of eight HRA alcohol‐related items, including the CAGE, weekly drinking quantity, and drinking and driving measures. We used Cohen's κ and Pearson's r to assess reliability and convergent validity. To assess criterion (predictive) validity, we used proportional hazards and logistical regression models predicting alcohol‐related hospitalizations and alcohol‐related separations from the Army, respectively.Results: A total of 404,966 soldiers completed an HRA. No particular demographic group seems to be over‐ or underrepresented. Although few respondents skipped alcohol items, those who did tended to be older and of minority race. The alcohol items demonstrate a reasonable degree of reliability, with Cronbach's α= 0.69 and test‐retest reliability associations in the 0.75–0.80 range for most items over 2‐ to 30‐day interims between surveys. The alcohol measures showed good criterion‐related validity: those consuming more than 21 drinks per week were at 6 times the risk for subsequent alcohol‐related hospitalization versus those who abstained from drinking (hazard ratio, 6.36; 95% confidence interval=5.79, 6.99). Those who said their friends worried about their drinking were almost 5 times more likely to be discharged due to alcoholism (risk ratio, 4.9; 95% confidence interval=4.00, 6.04) and 6 times more likely to experience an alcohol‐related hospitalization (hazard ratio, 6.24; 95% confidence interval=5.74, 6.77).Conclusions: The Army's HRA alcohol items seem to elicit reliable and valid responses. Because HRAs contain identifiers, alcohol use can be linked with subsequent health and occupational outcomes, making the HRA a useful epidemiological research tool. Associations between perceived peer opinions of drinking and subsequent problems deserve further exploration.
Alcohol Availability as a Predictor of Youth Drinking and Driving: A Hierarchical Analysis of Survey and Archival Data
Authors: Treno Andrew J. , Grube Joel W. , Martin Scott E. 
Published: November 2003

Background: Much attention has recently been directed toward developing preventive interventions to reduce drinking and driving through efforts to limit the numbers and locations of alcohol outlets at the community level. Although evaluations of these efforts have suggested linkages between alcohol outlets and problem outcomes, they have not addressed the linkage between outlets and drinking and driving among youth. The analysis reported here investigats the relationship between alcohol outlet densities and underage drinking and driving as self‐reported on two telephone surveys conducted in California.Methods: These analyses were based on data obtained from two telephone surveys conducted by the Prevention Research Center and archival data collected by the California Department of Alcoholic Beverage Control and the US Census Bureau. The sample for the first survey consisted of 15‐ to 20‐year‐old adolescents and young adults contacted by telephone, using a random digit dialing of exchanges in the greater San Francisco Bay Area. A second set of survey data was similarly collected by a random sample of households throughout California, and the Bay Area subset was also used for this analysis.Results: At the individual level, older respondents were more likely to report drinking and driving and riding with drinking drivers, whereas females and Asians were less so. At the aggregate or city‐level, alcohol outlet density, as measured by the number of on‐ and off‐premises establishments licensed to sell alcohol, was associated with both drinking and driving and riding with drinking drivers. These effects were moderated by a number of individual level effects, with younger respondents and females more likely to be affected by outlet densities.Conclusions: The findings here provide support for the implementation of policies targeting alcohol outlet density reductions. Areas with large numbers of such outlets provide ample opportunities to youth for alcohol purchases.
Protective Effect of Thalidomide on Endotoxin‐Induced Liver Injury
Authors: Enomoto Nobuyuki , Takei Yoshiyuki , Hirose Miyoko , Kitamura Tsuneo , Ikejima Kenichi , Sato Nobuhiro 
Published: November 2003

Background: Activation of Kupffer cells by lipopolysaccharide (LPS) plays a pivotal role in the onset of pathophysiological events that occur during endotoxemia, and intracellular calcium concentration ([Ca2+]i) is involved in LPS‐stimulated cytokine production. Tumor necrosis factor (TNF)‐α is produced exclusively by the monocyte‐macrophage lineage, which is mostly made up of Kupffer cells, and thalidomide has been shown to reduce TNF‐α production from macrophages. However, there is increasing evidence that TNF‐α may play a role in the initiation or progression of multiple organ failure syndrome. Therefore, the purpose of this work was to determine whether thalidomide could prevent LPS‐induced liver injury.Methods: Rats were given a single oral dose of thalidomide (5 mg/kg). To assess the sensitization of Kupffer cells, LPS (5 or 10 mg/kg) was administered intravenously, and mortality, liver histology, and transaminases were evaluated 24 hr later. Kupffer cells were isolated 2 hr after thalidomide treatment. After the addition of LPS, [Ca2+]i was measured by using a microspectrofluorometer with the fluorescent indicator fura‐2, and TNF‐α was measured by enzyme‐linked immunosorbent assay.Results: LPS caused focal necrosis with neutrophil infiltration in the liver. Moreover, LPS dramatically increased transaminases. These pathologic parameters and increases of serum transaminases were diminished markedly by thalidomide. In isolated Kupffer cells, LPS‐induced increases in [Ca2+]i and TNF‐α production were suppressed by treatment with thalidomide. To further explore the mechanism by which thalidomide directly abrogated Kupffer cell sensitivity to LPS, we determined the effect of thalidomide (5 μM) in vitro on LPS‐induced [Ca2+]i response and TNF‐α production. With the addition of thalidomide (5 μM) in vitro to the culture media for 2 hr before LPS, these parameters were suppressed.Conclusions: Thalidomide prevents LPS‐induced liver injury via mechanisms dependent on the suppression of TNF‐α production from Kupffer cells.
Dalteparin Sodium Prevents Liver Injury Due to Lipopolysaccharide in Rat Through Suppression of Tumor Necrosis Factor‐α Production by Kupffer Cells
Authors: Tsukada Shigeki , Enomoto Nobuyuki , Takei Yoshiyuki , Hirose Miyoko , Ikejima Kenichi , Kitamura Tsuneo , Sato Nobuhiro 
Published: November 2003

Background: Sensitization of Kupffer cells (KC) to lipopolysaccharide (LPS) and overproduction of tumor necrosis factor (TNF)‐α play important roles in the pathogenesis of alcoholic liver damage and sepsis‐associated organ injury. Therefore, suppression of TNF‐α should prove useful for treatment of LPS‐induced liver injury. Recently, heparin has been reported to diminish TNF‐α production from macrophages in response to LPS. Dalteparin sodium (DS) is a low‐molecular‐weight heparin with a mean molecular weight of 5000. DS elicits an antithrombotic effect through a mechanism depending on anti–factor Xa activity but not on the antithrombin activity. DS is thus suitable for treatment of disseminated intravascular coagulation because it has a much smaller prohemorrhagic property. In this study, we evaluated whether DS could prevent LPS‐induced liver injury.Methods: Female Wistar rats were administered DS (50 IU/kg intraperitoneally) followed by challenge with LPS (5 mg/kg intravenously) 2 hr later. Livers and sera were collected 24 hr later. KC from rats were isolated and cultured in RPMI 1640 supplemented with 10% fetal bovine serum. After the addition of LPS (10 μg/ml) to the culture media, intracellular Ca2+ was measured by using a fluorescent indicator, fura‐2.Results: LPS (5 mg/kg intravenously) caused focal necrosis and neutrophil infiltration in the control liver. The histological changes and increased alanine aminotransferase levels caused by LPS injection were diminished by treatment with DS. LPS increased intracellular Ca2+ of KC in control rats from the basal level (26 ± 6 nmol/liter) to 280 ± 18 nmol/liter. This increase was blunted by DS (126 ± 28 nmol/liter). The DS treatment decreased the LPS‐induced TNF‐α production by KC from 911 ± 78 pg/ml to 309 ± 45 pg/ml (p < 0.05).Conclusions: These results indicate that DS reduces the LPS‐induced liver injury through suppression of TNF‐α production.
Low Serum Amylase Levels in Drinking Alcoholics
Authors: Maruyama Katsuya , Takahashi Hisao , Okuyama Keiji , Yokoyama Akira , Nakamura Yuji , Kobayashi Yasunori , Ishii Hiromasa 
Published: November 2003

Background: We have reported that the serum level of amylase, different from other pancreatic enzymes, increases temporarily after abstinence in alcoholics. To elucidate the mechanism of this phenomenon, pancreatic isoamylase, salivary isoamylase, and amylase in urine were measured together with total serum amylase.Methods: Total serum amylase, pancreatic isoamylase, and salivary isoamylase values were measured in 38 male patients admitted to the National Alcoholism Center, Kurihama Hospital, for alcoholism after abstinence. In an investigation of amylase secretion, amylase in urine was measured in some patients after abstinence.Results: In the group with abnormally high total serum amylase on admission, levels were found to decrease after abstinence. In patients with pancreatic disorders in this group, abstinence leads to a decrease in total serum amylase, but in patients with no such disorders, total serum amylase increases temporarily due to increases in salivary isoamylase. In the group with normal total serum amylase on admission, levels increased sharply after abstinence, and both pancreatic isoamylase and salivary isoamylase contributed to the gains. In the group with low total serum amylase, a sharp increase of 2‐fold or more was noted after abstinence, and a major contributor was pancreatic isoamylase. The ratio of urine amylase to total serum amylase gradually declined, indicating clearly that abstinence led to a decrease in the excretion of amylase in urine.Conclusions: In cases of heavy alcohol consumption, a decrease in the production or secretion of pancreatic isoamylase and salivary isoamylase while drinking could happen. It was thus suggested that the increase in serum amylase might be due to the fact that this situation is improved by abstinence, plus the fact that excretion of amylase in urine increases during alcohol consumption, and abstinence brings about a decline in such excretion. Measurement of total serum amylase is not appropriate for diagnosing pancreatitis in alcoholic patients or those who consume large quantities of alcohol.
Accessibility of Alcohol‐Related Attitudes: A Cross‐Lag Panel Model With Young Adults
Authors: Kelly Adrian B. , Witkiewitz Katie 
Published: November 2003

Background: In the alcohol literature, most cognition research has focused on alcohol expectancies. Overall scores on alcohol expectancy questionnaires predict longitudinal changes in drinking behavior. However, the association between expectancy subscale scores and drinking behavior is inconsistent and modest. Attitudinal information may vary in accessibility (i.e., the ease or speed with which attitudinal information is evaluated), and more accessible (i.e., faster) attitudinal evaluations may predict heavier alcohol consumption. An alternative hypothesis arising from response competition theory is that heavy drinkers will show slow attitudinal evaluations, given that heavy drinkers frequently show mixed, inconsistent, or opposing alcohol‐related beliefs. In this study we examined the degree to which speed of processing of alcohol‐related evaluative judgments longitudinally predicted alcohol consumption in university students.Methods: Response latencies for alcohol‐ and non‐alcohol‐related attitudinal inquiries and measures of alcohol use were administered at two intervals 4 months apart.Results: The key findings were that response times for tension reduction and cognitive impairment items at time 1 positively predicted alcohol consumption at time 2. These results held after we accounted for autocorrelation in drinking and individual variability in reactivity.Conclusion: For items relating to tension reduction, response times fit a response competition hypothesis better than the attitude accessibility hypothesis.
Using the Cue‐Availability Paradigm to Assess Cue Reactivity
Authors: Davidson Dena , Tiffany Stephen T. , Johnston William , Flury Leah , Li Ting‐Kai 
Published: November 2003

Background: A recent meta‐analysis on cue‐reactivity research revealed that cue‐specific craving for alcohol is substantially less robust than craving measured for other drugs of abuse. The small effect sizes for alcohol underscore the need for more powerful methods of assessing cue reactivity in humans. The cue‐availability paradigm is a modification of the conventional cue‐reactivity paradigm and is intended to increase the sensitivity of measuring cue‐reactivity to alcohol in humans.Methods: Seventeen non‐treatment‐seeking alcoholics were tested individually on two different sessions (after priming with alcohol and after priming with placebo‐alcohol). Subjects were presented with a total of 32 cue‐availability trials. On each trial, subjects were presented with either a target cue (alcohol) or a neutral cue (water). Each cue was available for drinking on 50% of the trials (availability condition). Cue‐reactivity measures were self‐reports of craving and mood.Results: The alcohol prime had a robust effect on craving. Irrespective of the availability of the cue for consumption or the type of cue, craving was consistently higher when subjects were primed with alcohol than with placebo‐alcohol. Negative mood was also higher when it was assessed after the alcohol prime. Negative mood decreased in alcohol‐primed subjects when the alcohol cue was available for consumption. The alcohol cue also had a significant, although more modest effect on craving. The alcohol cue consistently elicited higher levels of craving relative to the water cue.Conclusions: These data suggest that the priming effects of alcohol may be a significant factor contributing to the experience of craving and maintenance of drinking. The study also introduces the cue‐availability as an additional new method for investigating manipulations of cue‐reactivity in alcoholics.
The Relationship Between Educational Attainment and Relapse Among Alcohol‐Dependent Men and Women: A Prospective Study
Authors: Greenfield Shelly F. , Sugarman Dawn E. , Muenz Larry R. , Patterson Marcus D. , He David Y. , Weiss Roger D. 
Published: November 2003

Background: We investigated the relationship between educational attainment and drinking outcomes after discharge from inpatient treatment for alcohol dependence.Methods: Between 1993 and 1996, we consecutively recruited 41 women and 60 men hospitalized for alcohol dependence and followed them up monthly for 1 year. We conducted structured interviews during hospitalization and at monthly intervals after discharge for 1 year. We examined the relationship between educational attainment before treatment and postdischarge drinking outcomes, including time to relapse.Results: After covariate adjustment, educational level was a significant predictor of drinking outcomes.Conclusions: Lower levels of educational attainment before entry into treatment predicted shorter times to first drink and relapse in both women and men. The association of educational attainment and treatment outcome for alcohol dependence warrants further investigation.