bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kindling of Withdrawal: A Study of Craving and Anxiety After Multiple Detoxifications in Alcoholic Inpatients
Authors: Duka Theodora , Townshend Julia M. , Collier Kirsty , Stephens David N. 
Published: April 2006

Background: The increased severity of withdrawal during successive detoxifications from alcohol is well documented for seizures, but the importance of the number of withdrawal events for other withdrawal symptoms such as anxiety and for alcohol craving is not known. Studies in animals are consistent with increases in reinforcing properties of alcohol with a greater number of withdrawal experiences. Thus, we predicted that patients who had undergone multiple detoxifications would show greater desire for alcohol and might experience more anxiety compared with patients with fewer detoxifications or compared with social drinkers.Methods: Forty‐two alcoholic inpatients were divided on the basis of medically supervised detoxifications into HI‐med (more than two previous detoxifications, n= 6) and LO‐med (two or fewer previous detoxifications, n= 36) and compared with a group of social drinkers matched for age, sex, and verbal IQ (n= 43). An additional analysis was performed by dividing the participants into HI‐total (n= 22) and LO‐total (n= 20) previous detoxification groups (three or more and less than three previous detoxifications, respectively) by using all previous detoxifications, which included unsupervised attempts. Anxiety was measured by Spielberger's State‐Trait Anxiety Inventory; mood was evaluated by using the Profile of Mood States; craving was evaluated with a short version of the Desire for Alcohol Questionnaire; and an emotional Stroop test was used that employed positive, negative, and alcohol‐related words.Results: When the analysis was based on the medically supervised detoxifications only, alcoholic participants (HI‐ and LO‐med) had higher ratings in trait anxiety and in feelings of anger, anxiety, depression, and confusion, but also friendliness; had higher craving ratings; and made more errors in the alcohol Stroop compared with social drinkers. In addition, the number of errors in the emotional Stroop for negative words was higher in the group with the higher number of detoxifications. When we analyzed the total number of detoxifications, this effect for the emotional Stroop errors was no longer seen. Instead, ratings of anger in the Profile of Mood States were greater in the HI‐total compared with the LO‐total detoxification group. These effects remained when the correlates alcohol consumption and degree of dependency were introduced as covariates, which showed that the effects found are probably attributable to the number of withdrawals.Conclusions: These data suggest that for inpatients with short history of alcoholism, the consequences of multiple withdrawals may not relate to anxiety or craving.
Temporal Discrimination Learning in Abstinent Chronic Alcoholics
Authors: McGlinchey‐Berroth Regina , Fortier Catherine B. , Cermak Laird S. , Disterhoft John F. 
Published: April 2006

Background: Converging evidence from varied experimental paradigms has demonstrated that the cerebellum is involved in the timing of learned behavior. Given the documented neurological changes secondary to chronic alcoholism, particularly cerebellar degeneration, the ability of recovered chronic alcoholics to learn a temporal discrimination was assessed by using delayed eyeblink classical conditioning.Methods: Twelve abstinent alcoholic participants and 12 matched control participants were randomly presented 2 clearly discriminable tone conditioned stimuli that were individually paired with 2 different interstimulus intervals.Results: The data revealed a significant alteration in the abstinent alcoholics’ peak latency measure at the long interstimulus intervals and an overall impairment in their level of acquisition of conditioned responses. No group differences in extinction were observed.Conclusions: It was speculated that cerebellar cortical atrophy caused by years of alcohol abuse resulted in the peak latency alteration and that atrophy extending into deep cerebellar nuclei caused the overall impairment in conditioned response acquisition.
Role of Acetaldehyde in the Discriminative Stimulus Effects of Ethanol
Authors: Quertemont Etienne , Grant Kathleen A. 
Published: April 2006

Background: Acetaldehyde has been suggested to mediate some of the effects of ethanol. Acetaldehyde can be produced by the enzyme catalase within the brain after ethanol administration. The catalase inhibitor 3‐amino‐1,2,4‐triazole (AT) reduces the production of acetaldehyde, and AT administration can reduce a number of ethanol‐induced behavioral effects; this suggests the involvement of acetaldehyde in these behaviors. However, a role for acetaldehyde in mediating the discriminative stimulus effects of ethanol remains unclear.Methods: The contribution of acetaldehyde to the discriminative stimulus effects of ethanol was investigated by use of a two‐lever drug discrimination paradigm with food reinforcement. Male Long‐Evans rats were trained to discriminate water from either 1.0 or 2.0 g/kg ethanol. Stimulus substitution tests were conducted with ethanol (0–2.5 g/kg by gavage) and acetaldehyde (0–300 mg/kg intraperitoneally). A cumulative dose‐response procedure was then used to investigate the effects of pretreatments with AT (0.5 and 1.0 g/kg intraperitoneally) on ethanol discrimination.Results: Acetaldehyde up to doses that decreased response rates (300 mg/kg) did not substitute for the discriminative stimulus effects of 1.0 or 2.0 g/kg ethanol. In addition, AT pretreatment did not affect the dose‐response curves for ethanol discrimination.Conclusions: These results show that exogenous acetaldehyde administration does not produce discriminative stimulus effects that are similar to those of ethanol. Also, pretreatment with the catalase inhibitor did not affect the dose‐response curve for ethanol discrimination, and this suggests that endogenously produced acetaldehyde does not contribute to the discriminative stimulus effects of ethanol. Together these results suggest that acetaldehyde does not mediate the discriminative stimulus effects of 1.0 to 2.0 g/kg ethanol.
Effects of Stress and Alcohol on Subjective State in Humans
Authors: Söderpalm Anna H. V. , de Wit Harriet 
Published: April 2006

Background: There is increasing evidence that stress and hypothalamic‐pituitary‐adrenal axis activation interact with drugs of abuse and influence drug‐taking behaviors. Both studies with laboratory animals and survey data with alcohol users suggest that acute or chronic stressful events increase alcohol intake. One mechanism for the increase in alcohol intake may be that stress alters the subjective effects produced by the drug in ways that enhance the reinforcing properties of alcohol. Therefore, in this study we determined whether an acute social stressor alters subjective responses to ethanol in humans. The stressor was a modified version of the Trier Social Stress Test, an arithmetic task that increases cortisol levels.Methods: Twenty male volunteers participated in two laboratory sessions, in which they performed the Trier Social Stress Test on one session and no task on the other session, immediately before consuming a beverage that contained ethanol (0.8 g/kg in juice) or placebo (juice alone). Eleven subjects received ethanol on both sessions, and nine subjects received placebo on both sessions. Primary dependent measures were self‐report questionnaires of mood states. Salivary levels of cortisol were obtained to confirm the effectiveness of the stress procedure.Results: Stress alone produced stimulant‐like subjective effects. In the group who received ethanol, stress increased sedative‐like effects and decreased stimulant‐like effects.Conclusions: At this relatively high dose of ethanol, stress increased sedative effects of alcohol and did not increase desire for more alcohol. It is possible that in some individuals, the increased sedative effects after stress may increase the likelihood of consuming more alcohol. The effects of stress on consumption at this, or lower, doses of alcohol remain to be determined.
Biphasic Alcohol Response Differs in Heavy Versus Light Drinkers
Authors: King Andrea C. , Houle Tim , de Wit Harriet , Holdstock Louis , Schuster Alyson 
Published: April 2006

Background: Most studies of risk factors for alcohol‐related problems have focused on biological family history as a primary risk factor. However, other factors, such as early‐age heavy drinking, are also risk factors for sustained or progressive heavy consumption. Little is currently known about the mechanisms underlying binge or heavy drinking.Methods: This study examined the acute subjective and objective effects of ethanol in heavy drinkers versus light drinkers. Thirty‐four subjects participated in this within‐subjects study consisting of three early‐evening testing sessions in which subjects consumed a beverage containing either 0.8 or 0.4 g/kg ethanol or placebo.Results: Compared with lighter drinkers, heavy drinkers were more sensitive to the positive stimulant‐like effects of ethanol (p < 0.05), especially during the increasing limb of the blood alcohol curve. Heavy drinkers also showed less sedation and cortisol response after alcohol than the light drinkers (p < 0.05).Conclusions: The results indicate that young adult binge drinkers show a biphasic alcohol response, with heightened sensitivity to stimulant‐like alcohol effects and greater tolerance to sedative alcohol effects compared with their light‐drinking counterparts.
Preoperative Evaluation of Chronic Alcoholics Assessed for Surgery of the Upper Digestive Tract
Authors: Martin M. J. , Heymann C. , Neumann T. , Schmidt L. , Soost F. , Mazurek B. , Böhm B. , Marks C. , Helling K. , Lenzenhuber E. , Müller C. , Kox W. J. , Spies C. D. 
Published: April 2006

Background: Alcoholics are at risk of developing major complications in the postoperative period. Adequate prophylactic treatment, as well as preoperative abstinence, can significantly decrease the rate of complications. However, the preoperative diagnosis of alcoholism is difficult to establish. The purpose of this study was to assess whether three preoperative visits, an alcohol‐related questionnaire (CAGE), and the laboratory markers carbohydrate‐deficient transferrin (CDT) and γ‐glutamyltransferase (GGT) would increase the rate of detection of chronic alcoholics.Methods: The study included the Departments of ENT, Facial and Maxillofacial Surgery, and General Surgery of a university hospital; 705 male patients were assessed for tumor surgery of the upper digestive tract and were allocated to 5 different groups. All patients were seen three times, and five different strategies were used to detect chronic alcoholics. The gold standard was the diagnosis of alcohol misuse made by an experienced (blinded) investigator according to the DSM‐III‐R. The main outcome measurements were the detection rates of the different test strategies.Results: By clinical routine alone, only 16% were detected during the first visit and 34% after three visits. If the CAGE questionnaire was added, sensitivity increased to 64%. The further addition of GGT or CDT led to 80 and 85% detections, respectively. A combination of all tests had a sensitivity of 91%.Conclusions: To detect more alcoholic patients at risk for major complications, patients should be seen more often, and additional diagnostic tools such as the CAGE, CDT, and GGT should be used before surgery.
The Genetics of Alcoholism in Polynesians: Alcohol and Aldehyde Dehydrogenase Genotypes in Young Men
Authors: Chambers Geoffrey K. , Marshall Stephen J. , Robinson Geoffrey M. , Maguire Sean , Newton‐Howes Jan , Chong Nicola L. 
Published: April 2006

Background The last 10 years have seen growing recognition of the significance of the genes encoding enzymes responsible for hepatic alcohol metabolism as protective factors in the development of alcoholism.Methods We have developed DNA sequencing assays for measuring genetic variation at the alcohol dehydrogenase2 (ADH2), ADH3, and aldehyde dehydrogenase 2 (ALDH2) loci. These have been used to survey volunteer control subjects from three New Zealand ethnic groups (white, Asian, and Polynesian) and young male alcoholics recruited from white and New Zealand Maori patients in a local treatment program.Results The allele frequency values for whites and Asians obtained in our study closely match those obtained previously in other laboratories. Our data (the first for Polynesians) are 0.42 for ADH2*2, 0.78 for ADH3*1, and 0.00 for ALDH2*2. In the New Zealand Maori alcoholic patients, the ADH2*2 frequency is significantly lower (0.15;p < 0.01). The frequency of ADH3*1 is also lower in this group (0.60), but this value is not significant (0.05 <p < 0.06).Conclusions In young male New Zealand Maori, the ADH2*2 allele is a protective factor against alcoholism even in the absence of ALDH2*2.
The Effect of Tryptophan Depletion on Alcohol Self‐Administration in Non‐Treatment‐Seeking Alcoholic Individuals
Authors: Petrakis Ismene L. , Buonopane Alessandra , O'Malley Stephanie , Cermik Omer , Trevisan Louis , Boutros Nashaat N. , Limoncelli Diana , Krystal John H. 
Published: April 2006

Background Alcohol self‐administration in the laboratory has been used to evaluate pharmacological treatments and neurobiological mechanisms that underlie alcohol use in alcohol‐dependent individuals. This study evaluated whether attenuation of serotonin synthesis via depletion of its precursor tryptophan reduces the amount of alcohol consumed in a self‐administration paradigm in non‐treatment‐seeking individuals with alcohol use disorders.Methods Individuals with alcohol dependence (n= 8) and alcohol abuse (n= 4) who were not seeking treatment were recruited by advertisement and participated in two test days, 1 week apart. Each test session was preceded by administration of a concentrated amino acid drink that resulted in a rapid and significant decline in plasma free tryptophan (active depletion) or a similar drink containing tryptophan (placebo depletion). Tests were conducted in a randomized, double‐blind fashion. The test session began with a cue exposure session where subjects were exposed to their favorite alcoholic beverage and asked to rate their craving for alcohol. After this, subjects were administered a priming drink designed to raise blood alcohol levels to 0.02 g%. Subjects then had the opportunity to drink up to eight additional drinks, each designed to raise blood alcohol levels by 0.02 g%, or to receive $3 for each drink not consumed over a 2‐hr period.Results There were no significant differences in alcohol consumed or subjective intoxication with active tryptophan depletion compared with placebo. Self‐reported craving correlated with the amount of alcohol consumed in the session.Conclusions These data question the dependence of alcohol self‐administration on the ongoing synthesis of serotonin.
The Five‐Year Predictive Validity of Each of the Seven DSM‐IV Items for Alcohol Dependence Among Alcoholics
Authors: Schuckit Marc A. , Danko George P. , Smith Tom L. , Buckman Kelly R. 
Published: April 2006

Background Information about the prognostic implications of a DSM‐IV diagnosis of alcohol dependence is important to both clinicians and researchers. In this regard, only limited data are available on the performance of specific diagnostic items.Methods This study reports data gathered with a structured, validated interview with 642 alcohol‐dependent men and women from the Collaborative Study of the Genetics of Alcoholism (COGA). The goals were to evaluate the ability of each of the DSM‐IV dependence items to predict the occurrence over the next 5 years of a broad pattern of 27 alcohol‐related problems. For comparison, similar data are reported regarding the performance of abuse criteria for 516 additional subjects.Results The results revealed that dependence item 3 (use of alcohol in larger amounts) was the only criterion that did not relate significantly to outcome, and indicated that the dependence criteria related relatively similarly to different types of outcomes among alcoholics. No specific combination of diagnostic items stood out in predicting outcome but, rather, the span of items generally performed well.Conclusions These data support the potential usefulness of the DSM‐IV dependence criteria.
Relationship of Light to Moderate Alcohol Consumption and Risk of Hypertension in Japanese Male Office Workers
Authors: Nakanishi Noriyuki , Makino Kae , Nishina Kazue , Suzuki Kenji , Tatara Kozo 
Published: April 2006

Background A close relationship between alcohol consumption and hypertension has been established, but the effect of light to moderate alcohol consumption on blood pressure (BP) remains unclear.Methods A total of 5275 Japanese male office workers aged 23 to 59 years partook in a survey. Subjects were classified as nondrinkers or current drinkers who averaged less than 12, 12 to 22, 23 to 45, or ≥46 g/day of ethanol. BPs were measured at annual health examinations from May 1996 through May 2000. A total of 3784 hypertension‐free (systolic BP <140 mm Hg, diastolic BP <90 mm Hg, no medication for hypertension, and no history of hypertension) men were observed for 4 years. Men in whom hypertension (systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg, or both or receipt of antihypertensive medication) was found during repeated surveys were defined as incident cases of hypertension.Results After controlling for potential predictors of hypertension, systolic and diastolic BP levels and the incidence of hypertension were lowest in nondrinkers in all three age ranges (23–35, 36–47, and 45–59 years) and increased in a dose‐dependent manner as alcohol consumption increased. For individuals aged 23 to 35 years, systolic and diastolic BP levels and the incidence of hypertension were significantly higher among those who drank an average of ≥23 g/day of ethanol than among nondrinkers. For those aged 36 to 59, the diastolic BP level was significantly higher among those who drank any alcohol at all than among nondrinkers, and the systolic BP level and the incidence of hypertension were significantly higher among those who drank an average of ≥12 g/day of ethanol than among nondrinkers.Conclusions Light to moderate alcohol consumption seems to have an important influence on BP in both young and middle‐aged Japanese men.
Alterations in Insulin‐Like Growth Factor‐I Signaling in Cardiomyocytes From Chronic Alcohol‐Exposed Rats
Authors: Pecherskaya Anna , Rubin Emanuel , Solem Michele 
Published: April 2006

Background Insulin‐like growth factor‐I (IGF‐I) is a required cytokine for the development and maintenance of the cardiovascular system, and it may play a role in certain pathophysiological conditions.Methods Adult male rats were fed a liquid diet that contained 36% alcohol for 4 to 8 months, and their littermates served as isocaloric pair‐fed controls, so we could examine IGF‐I signaling in rat cardiomyocyte preparations.Results Recently, our laboratory reported that IGF‐I activates protein kinase‐C (PKC)‐α and that PKC‐α activity is required for IGF‐I‐dependent activation of Erk1/Erk2 and IGF‐I‐dependent protein synthesis. But in chronic alcohol‐exposed rats, there is loss of PKC‐α activation by IGF‐I, represented as a reduction in PKC‐α translocation to the membrane. In reverse transcription‐polymerase chain reaction experiments, both the alcoholic and control animals expressed the IGF‐I receptor (IGF‐1R, α subunit) and IGF‐I mRNAs in approximately equal amounts. However, in the alcoholic cardiomyocyte protein preparations, there was a higher basal level of IGF‐1R autophosphorylation of its internal tyrosine kinase domain, and IGF‐I‐activated autophosphorylation was reduced in the alcoholic protein preparations. Previously, we have demonstrated that acute IGF‐I exposure enhances the rate of Mn2+ influx through activated nitrendipine‐sensitive cardiac Ca2+ channels, and that this enhancement of channel activity is PKC‐dependent. Here, we report that in alcohol‐exposed myocytes, IGF‐I‐induced augmentation of the cardiac Ca2+ channel activity was absent. IGF‐I increased the rate of protein synthesis in the control animals by 56% as determined in protein synthesis experiments that measured the rate of 14C‐L‐phenylalanine incorporation over time, and this effect was blocked by preincubation with Gö6976, a specific inhibitor of PKC‐α. However, in the alcohol‐exposed cardiomyocytes, IGF‐I did not increase the rate of protein synthesis.Conclusion These results suggest that IGF‐I‐dependent PKC‐α activation and IGF‐I‐dependent protein synthesis are altered in the hearts of chronic alcohol‐exposed rats. This may be the result of the IGF‐1R being in a chronically activated state, and it may alter the normal function of PKC‐α.
Melatonin (an Antioxidant) Does Not Ameliorate Alcohol‐Induced Purkinje Cell Loss in the Developing Cerebellum
Authors: Edwards Russell B. , Manzana Ehrine J. P. , Chen Wei‐Jung A. 
Published: April 2006

Background One popular mechanism proposed to account for alcohol‐induced brain damage is the generation of free radicals after alcohol exposure. Therefore, it is reasonable to hypothesize that administration of an antioxidant should reduce the severity of alcohol‐induced brain damage. Recently, melatonin has been shown to be an effective free‐radical scavenger. In this study, the ability of melatonin to attenuate alcohol‐induced cerebellar Purkinje cell loss in the cerebellar vermis and lobule I was assessed.Methods Sprague‐Dawley rat pups were used in this study. These neonatal pups were exposed to alcohol (4.5 g/kg), melatonin (10 mg/kg), both alcohol and melatonin, or control vehicle via artificial‐rearing methods from postnatal day (PD) 4 to PD 9. Alcohol, melatonin, or control vehicle was mixed with milk formula in 2 of the daily 12 feedings. Pups were killed 90 min after the beginning of the second alcohol feeding on PD 9.Results Alcohol significantly reduced the Purkinje cell numbers in the vermis and lobule I, with a higher percentage of cell loss in lobule I compared with the vermis. However, melatonin, per se, neither affected the Purkinje cell number nor diminished alcohol‐induced Purkinje cell loss.Conclusions Melatonin was not effective in attenuating alcohol‐induced loss of Purkinje cells in our neonatal rat model system, even though such a dosage of melatonin is capable of reversing free radical–induced damage in other tissues.