bluuebunny/crossref_metadata_2025 huggingface dataset:
Real‐Time Assessments of Dopamine Function during Behavior: Single‐Unit Recording, Iontophoresis, and Fast‐Scan Cyclic Voltammetry in Awake, Unrestrained Rats
Authors: Rebec George V.
Published: May 2006

Although ample evidence implicates the dopamine (DA) projection to the neostriatum and nucleus accumbens in motor and motivational processes, relatively little information is available on how DA alters neostriatal or accumbal functions under naturally occurring behavioral conditions. Further insight into neuron‐behavior relationships can be achieved with the application of single‐unit recording techniques, including iontophoresis and fast‐scan cyclic voltammetry (FSCV), to awake, unrestrained animals. Single‐unit recording has revealed that amphetamine, a widely abused psychomotor stimulant, activates motor‐, but inhibits nonmotor‐related neurons in neostriatum and nucleus accumbens. Although either response can be blocked by DA receptor antagonists, the amphetamine‐induced activation also depends on an intact corticostriatal system, suggesting a role for glutamate (GLU). Both neostriatal and accumbal neurons are sensitive to iontophoretic application of either DA or GLU, but when applied during low‐dose application of DA, the GLU signal is enhanced relative to background activity. In effect, DA appears to modulate GLU by strengthening the GLU signal‐to‐noise ratio. To assess DA release under behaviorally relevant conditions, FSCV has been used to obtain real‐time measurements of DA efflux in a free‐choice novelty test. DA efflux increased only during the brief period of entry into novelty, and the increase was confined to accumbal shell and the shell‐core transition zone, the so‐called shore. Neither accumbal core nor the overlying neostriatum showed a novelty‐related DA change. Thus, DA release during behavior is not uniform and in the case of novelty appears targeted to the limbic‐related area of accumbal shell. Further application of these and other in vivo technologies to ambulant animals is required to identify the complex mechanisms underlying both the release of DA and its effect on neostriatal and accumbal neurons during behavior.
Metabolic Mapping of the Effects of Oral Alcohol Self‐Administration in Rats
Authors: Porrino Linda J. , Williams‐Hemby Lisa , Whitlow Christopher , Bowen Carrie , Samson Herman H.
Published: May 2006

The functional effects of the voluntary consumption of ethanol in rats were investigated using the quantitative autoradiographic 2‐[14C]deoxyglucose method for measurement of rates of local cerebral glucose utilization. A modified sucrose‐substitution procedure was used to train three groups of Wistar rats to self‐administer water, a 5% sucrose solution, or a 10% ethanol/5% sucrose solution in daily sessions. Once stable rates of consumption were established, the 2‐[14C]deoxyglucose method was applied immediately after completion of the final test session. Rats received a dose of ethanol equivalent to 0.5 g/kg (n= 6) on the day of the procedure or a comparable volume of sucrose solution (n= 6) or water (n= 5). Rates of local cerebral glucose utilization in rats that ingested water did not differ from those that rats consumed a 5% sucrose solution. In contrast, voluntary ethanol consumption produced a highly discrete pattern of changes in rates of glucose utilization. Ethanol ingestion increased cerebral metabolism, as compared with rates of metabolism in rats that consumed either water or sucrose in the rostral pole and shell of the nucleus accumbens, medial prefrontal cortex, lateral septum, basolateral and central nuclei of the amygdala, substantia nigra, and the ventral tegmental area. This pattern of alterations in functional activity is distinctly different from that observed when equivalent doses of ethanol are administered acutely, emphasizing the importance of self‐administration in determining the changes in glucose utilization. Furthermore, within the nucleus accumbens, glucose utilization was selectively augmented in the rostral pole and shell subterritories, whereas cerebral metabolism in the core was unaffected. Finally, these data demonstrate that it is the simultaneous activation of an interconnected network of limbic brain regions that serves as the substrate of the effects of voluntarily ingested ethanol.
Interleukin‐12 Therapy Restores Cell‐Mediated Immunity in Ethanol‐Consuming Mice
Authors: Peterson Jeffrey D. , Vasquez Kristine , Waltenbaugh Carl
Published: May 2006

Previous studies from our laboratory show that ethanol consumption impairs antigen‐specific, cell‐mediated, but not, humoral immune responses of C57BL/6, BALB/c, and D011.10 T‐cell receptor transgenic mice. This ethanol‐associated deficit is associated with decreased interleukin (IL)‐12 and interferon–γ (IFN‐γ) production, but not IL‐2 or antigen‐specific T‐cell proliferation by explanted leukocytes from ethanol‐consuming mice. IL‐12 expression by macrophage/monocytes is viewed as a requirement for the production of IFN‐γ by Th1 lymphocytes that mediate cellular immunity. In this study, we restored antigen‐specific, cell‐mediated immunity, delayed hypersensitivity, to ethanol‐consuming C57BL/6 or BALB/c mice with a single 100 ng of intravenous injection of recombinant IL‐12 at the time of immunization. The addition of exogenous recombinant IL‐12 to co‐cultures of antigen‐presenting cells derived from ethanol‐consuming mice and purified T cells derived from ethanol‐nonconsuming DO11.10 repairs the ability of Th1 cells to make IFN‐γ in response to antigen. Administration of recombinant IL‐12 opens a potential for restoring cell‐mediated immune function to ethanol‐consuming individuals.
Long‐Term Outcome of Children with Fetal Alcohol Syndrome: Psychopathology, Behavior, and Intelligence
Authors: Steinhausen Hans‐Christoph , Spohr Hans‐Ludwig
Published: May 2006

Within an interdisciplinary research project, the long‐term outcome of children with fetal alcohol syndrome was studied. Methods for the assessment of psychopathology, behavior, and intelligence included psychiatric interviews, behavior checklists for parents and teachers, and intelligence tests. The children were assessed during preschool age, early school age (6 to 12 years), and late school age (≥ 13 years). An excess of psychopathology, (including hyperkinetic disorders, emotional disorders, sleep disorders, and abnormal habits and sterotypies) with a strong persistence over time was found. Cognitive functioning was marked by a large proportion of mentally retarded children and also did not change considerably over time. This long‐term outcome study reflects the handicapping effects of fetal alcohol syndrome.
Ethanol Reward and Aversion in Mice Bred for Sensitivity to Ethanol Withdrawal
Authors: Chester Julia A. , Risinger Fred O. , Cunningham Christopher L.
Published: May 2006

The present study examined mice selectively bred for sensitivity to ethanol withdrawal for differences in the conditioned place preference (CPP) and conditioned taste aversion (CTA) paradigms. Withdrawal Seizure‐Prone (WSP) and Withdrawal Seizure‐Resistant (WSR) mice and High Alcohol Withdrawal (HAW) and Low Alcohol Withdrawal (LAW) mice were selectively bred for differences in chronic and acute ethanol withdrawal, respectively. For the CPP experiment, male HAW and LAW (generation 5) mice received four pairings of ethanol (2g/kg), with a distinctive floor stimulus. On intervening days, mice received saline paired with an alternate floor type. During the preference test, all mice received an injection of saline before 60‐min access to both floor types. HAW mice showed conditioned preference for the ethanol‐paired floor, whereas LAW mice did not. For the CTA experiments, male HAW, LAW, WSP, and WSR mice were adapted to a 2‐hr/day water restriction regimen and subsequently received ethanol injections (0, 2, 2.5, or 4 g/kg, ip) immediately after 1‐hr access to a NaCl‐flavored solution. Dose‐dependent reductions in NaCl intake reflected the development of CTA in both HAW/LAW and WSP/WSR lines. However, a smaller magnitude of CTA was observed in WSP mice relative to WSR mice after the first ethanol‐NaCl pairing. WSP/WSR mice showed similar reductions of NaCl intake on subsequent conditioning trials. Overall, these data suggest that HAW mice selectively bred for high sensitivity to acute ethanol withdrawal are more sensitive to the rewarding effects of ethanol in the CPP paradigm. This outcome is consistent with a previous study showing greater CPP in WSP mice relative to WSR mice. In the CTA paradigm, sensitivity to ethanol withdrawal in the HAW/ LAW selected lines does not appear to be genetically correlated with sensitivity to the aversive properties of ethanol. However, the difference in acquisition of CTA in WSP/WSR lines suggest that some genes determining ethanol withdrawal severity may also influence initial sensitivity to ethanol's aversive effects.
Comparison of Social Abilities of Children with Fetal Alcohol Syndrome to Those of Children with Similar IQ Scores and Normal Controls
Authors: Thomas Suzanne E. , Kelly Sandra J. , Mattson Sarah N. , Riley Edward P.
Published: May 2006

Children diagnosed with fetal alcohol syndrome (FAS) were assessed with items from the social skills domain of the Vineland Adaptive Behavior Scales (VABS) via interviews with their caregivers. Their scores were compared with scores from children in two control groups. The control groups included children matched for IQ to the FAS group (specifically on verbal IQ, henceforth, the VIQ group) and children with IQ scores in the average to above‐average range (normal control group). Forty‐five children (age range, 5 years 7 months to 12 years 11 months) were assessed (n/group = 15). All groups differed with regard to social ability, as measured by the VABS (NC > VIQ > FAS), even when the effects of socioeconomic status were held constant. The three subdomains of the VABS social scale (interpersonal relationship skills, use of play and leisure time, and coping skills) were assessed, and results showed that the children with FAS were most impaired on the subdomain that assessed interpersonal relationship skills. An additional measure was constructed by obtaining an age‐equivalent score for the VABS social scale and calculating a difference score by subtracting the child's chronological age from his/her age‐equivalent score. There was a significant correlation between chronological age and difference scores for children in the FAS group but not for children in the two control groups. Specifically, in older children with FAS, there was an increased discrepancy between their ages and their age‐equivalent scores, a discrepancy that was not present in children in the control groups. These results suggest that social deficits in children with FAS are beyond what can be explained by low IQ scores and indicate that there may be arrested, and not simply delayed, development of social abilities in children with FAS.
Participant Selection Biases in a Randomized Clinical Trial of Alcoholism Treatment Settings and Intensities
Authors: Rychtarik Robert G. , McGillicuddy Neil B. , Connors Gerard J. , Whitney Robert B.
Published: May 2006

Eligible participants and decliners in a randomized study of inpatient, intense outpatient, and standard outpatient treatments for alcoholics were compared and contrasted on a series of demographic, social stability, psychological, legal, drug use, problem severity, and treatment history variables. Among 302 individuals meeting eligibility requirements, those agreeing to participate, compared with decliners, were more likely to be unemployed, be residentially less stable, have legal problems, use other drugs, have a more severe alcohol problem, have a recent treatment history, and were less likely to have problems with violence. Participants also were more likely to be male and non‐white, although gender and racial effects were not significant when other variables were controlled for. The implications of these findings for generalizing the results of inpatient‐outpatient studies are discussed, and the need for routine reporting of decliner characteristics in research reports is stressed.
Sustained‐Release Naltrexone for Alcoholism Treatment: A Preliminary Study
Authors: Kranzler Henry R. , Modesto‐Lowe Vania , Nuwayser Elie S.
Published: May 2006

This 12‐week study examined the bioavailability, tolerability, and potential efficacy of an injectable sustained‐release preparation (SRP) of naltrexone (NTX). Twenty alcohol‐dependent subjects took NTX 50 mg po daily for 2 weeks, followed by a 2‐week, no‐medication Washout Period, a 4‐week Injection Period, and a 4‐week Follow‐up Period. Fifteen subjects (75%) received a single subcutaneous injection of 206 mg of sustained‐release NTX, and five subjects (25%) received a placebo injection. All subjects also received eight weekly coping skills sessions during the Oral NTX, and the Washout and Injection Periods. Results: After injection, NTX plasma concentrations exceeded a mean of 1 ng/ml for 21 days. Adverse effects produced by the SRP of NTX were comparable with those resulting from oral NTX therapy. Compared with placebo, the SRP of NTX significantly reduced the frequency of heavy drinking days during the Injection and Follow‐up Periods. Conclusions: The results of this preliminary study support the potential clinical utility of the SRP of NTX for treatment of alcohol dependence.
Microsomal Acetaldehyde Oxidation is Negligible in the Presence of Ethanol
Authors: Wu Yue‐Sheng , Salmela Katja S. , Lieber Charles S.
Published: May 2006

The microsomal ethanol oxidizing system (MEOS), inducible by ethanol and acetone, oxidizes ethanol to acetaldehyde, which causes many toxic effects associated with excess ethanol. Recent studies reported that rat liver microsomes also oxidize acetaldehyde, thereby challenging the validity of the assessment of MEOS activity by measuring acetaldehyde production and suggesting that MEOS activity results in the accumulation not of acetaldehyde but, rather, of its less toxic metabolite, acetate. To address these issues, we compared both metabolic rates of ethanol and acetaldehyde and the effect of ethanol on the acetaldehyde metabolism.

Liver microsomes were prepared from Sprague‐Dawley rats induced either with acetone for 3 days or ethanol for 3 weeks. NADPH‐dependent acetaldehyde (300 /μM) metabolism was measured in two ways: (1) by detection of acetaldehyde disappearance by headspace gas chromatography, and (2) by assessment of acetaldehyde oxidation by liquid scintillation counting of acetate formed from [1,2‐14C]acetaldehyde. Ethanol (50 mM) oxidation was measured by gas chromatography. In acetone‐ and ethanol‐induced rat liver microsomes, the acetaldehyde disappearance (p< 0.0001) and oxidation (p< 0.0001) rates were both significantly increased. The rates of acetaldehyde oxidation paralleled those ofp‐nitrophenol hydroxylation (r= 0.974,p< 0.0001), with a Kmof 82 ± 14 μM and a Vmaxof 4.8 ± 0.5 nmol/min/mg protein in acetone‐induced microsomes. Acetaldehyde disappearance in acetone‐induced microsomes and acetaldehyde oxidation in acetone‐induced and ethanol‐induced microsomes were significantly lower than the corresponding ethanol oxidation, with rates (nmol/min/mg protein) of 4.6 ± 0.6 versus 9.0 ± 0.8 (p< 0.005), 4.4 ± 0.3 versus 9.1 ± 0.5 (p< 0.0005), and 14.0 ± 0.9 versus 19.5 ± 1.8 (p< 0.05), respectively. The presence of 50 mM ethanol decreased this metabolism to 0.9 ± 0.3 (p< 0.005), 0.5 ± 0.1 (p< 0.001), and 1.8 ± 0.3 (p< 0.001), resulting in rates of acetaldehyde metabolism of only 9.8 ± 3.2%, 6.0 ± 0.5%, and 9.5 ± 1.2% (respectively) of those of ethanol oxidation.

In conclusion, rat liver microsomes oxidize acetaldehyde at much lower rates than ethanol, and this acetaldehyde metabolism is strikingly inhibited by ethanol. Accordingly, acetaldehyde formation provides an accurate assessment of MEOS activity. Furthermore, because acetaldehyde production vastly exceeds its oxidation, the net result of MEOS activity is the accumulation of this toxic metabolite.
Do Taste Factors Contribute to the Mediation of Ethanol Intake? Ethanol and Saccharin‐Quinine Intake in Three Rat Strains
Authors: Goodwin Frances L. W. , Amit Zalman
Published: May 2006

Several recent studies have suggested that ethanol‐preferring rodents may also have an affinity for sweet solutions (saccharin, sucrose) and, conversely, that saccharin preference may predict ethanol preference. The purpose of the present investigation was to determine whether intake of ethanol and saccharin‐quinine (SQ) solutions would be related in three nonselected strains of rats who differ in their ethanol preference: Lewis, Wistar Kyoto, and Wistar. In the first phase of the experiment, all animals were presented with an ascending series of ethanol solutions (2 to 10%) in free choice with water, followed by a 10‐day maintenance period of 10% ethanol with water. In the second phase, the same animals were presented with an ascending series of SQ solutions (saccharin: 0.4%. quinine: 0.001 to 0.04%) in free choice with water, followed by a 10‐day maintenance period of 0.4% saccharin with 0.04% quinine and water. The results revealed an absence of a direct relationship between ethanol and SQ consumption. The ethanol‐nonpreferring Lewis rats showed a greater preference for the SQ solutions than Wistar Kyoto rats, whereas the ethanol‐preferring Wistar Kyoto strain consistently consumed significantly less SQ. Wistar rats showed relatively stable consumption levels for both solutions that fell between those of the other two strains. These results suggested that the relationship between ethanol and SQ preference in rats was not a direct one and did not support the findings in the literature of a simple overall positive relationship between sweet and ethanol preference. These data do, however, provide further evidence for taste factors in the mediation of self‐selection of ethanol in rats.
The Specificity of the CDT Assay in General Practice: The Influence of Common Chronic Diseases and Medication on the Serum CDT Concentration
Authors: Meerkerk G‐J. , Njoo K. H. , Bongers I. M. B. , Trienekens P. , van Oers J. A. M.
Published: May 2006

Early recognition of alcohol problems by general practitioners might be enhanced by the use of better alcohol markers. Several studies have revealed promising results for the carbohydrate‐deficient transferrin (CDT) assay in certain populations. The aim of our study was to examine the specificity of the CDT assay in a general practice population. The main research question was whether common chronic diseases and/or the accompanying prescribed drugs have a negative influence on the specificity of the CDT assay. The 524 men who participated were selected from seven general practices and were suffering from one or more of the following diseases: hypertension, asthma/bronchitis, diabetes mellitus, adipositis/lipid metabolism disorder, angina pectoris, depression, and disorders of the digestive tract. None of the studied diseases or of the accompanying prescribed drugs had an influence on the specificity of the CDT assay. The overall specificity in this general practitioner population was 0.92. It can be concluded that the studied diseases do not bear an influence on the serum CDT concentration, and that, therefore, the CDT assay is a highly specific instrument for use in assessing alcohol consumption in general practice patients.
Prevalence of Alcohol Dependence and Abuse in General Practice
Authors: Hill Andreas , Rumpf Hans‐Jürgen , Hapke Ulfert , Driessen Martin , John Ulrich
Published: May 2006

The aim of this study is to deliver representative epidemiological data about the prevalence of alcohol abuse and dependence in general practices in an urban area. In 12 general practices at Luebeck, a Northern German city with 220,000 inhabitants, a total of 929 patients (aged between 14 and 75 years) were screened using the CAGE and the Short Michigan Alcoholism Screening Test. If one of these screening questionnaires or the General Practitioners' assessment of the patient indicated an alcohol problem, the patient underwent a standardized diagnostic interview using the alcohol section of the Schedules for Clinical Assessment in Neuropsychiatry. The prevalence rates according to ICD‐10 or DSM‐III‐R were 3.5% for alcohol abuse and 7.2% for alcohol dependence, the sex ratio was 1:2.8 (fema1e:male). These results are compared with previous findings, and general epidemiological implications of this study are discussed.
Modulation of Volitional Ethanol Intake in the Rat by Central δ‐Opioid Receptors
Authors: Franck Johan , Lindholm Sara , Raaschou Pauline
Published: May 2006

The acute effect of opioid antagonists on volitional ethanol intake was studied in unselected Sprague‐Dawley rats using a two‐bottle, free‐choice model. The total daily intake of ethanol during saline treatment was 1.79 ± 0.4 g/kg/day (n= 136). The rats were deprived of fluids for the last 4 hr of the light period. Saline or drug was given intraperitoneally 20 to 30 min before the onset of dark, and the ethanol and water intakes were measured during the following hour. The ethanol intake during this hour was 0.75 ± 0.06 g/kg (n= 136). Naltrexone significantly reduced ethanol intake. There was also a signiflcant reduction in ethanol Intake following administration of ICI‐174,864. Naloxonazine and naloxone methiodide lacked effect. None of the treatments had any effect on the water or food intake. The resutts suggest that central bopioid receptors modulate volitional ethanol intake in the rat.
Identification of the Human P‐450 Enzymes Responsible for the Sulfoxidation and Thiono‐Oxidation of Diethyldithiocarbamate Methyl Ester: Role of P‐450 Enzymes in Disulfiram Bioactivation
Authors: Madan Ajay , Parkinson Andrew , Faiman Morris D.
Published: May 2006

Diethyldithiocarbamate methyl ester (DDTC‐Me) is a precursor to the formation of S‐methyl‐N,N‐diethyliolcarbamate sulfoxide, the active metabolite proposed to be responsible for the alcohol deterrent effects of disulfiram. The present study investigated the role of human cytochrome P‐450 (CYP) enzymes in sulfoxidation and thiono‐oxidation of DDTC‐Me, intermediary steps in the activation of disulfiram. Several approaches were used in an attempt to delineate the particular P‐450 enzyme(s) involved in the sulfoxidation and thiono‐oxidation of DDTC‐Me. These approaches included the use of cDNA‐expressed human P‐450 enzymes, correlation analysis with sample‐to‐sample variation in human P‐450 enzymes in a bank of human liver microsomes, and chemical and antibody inhibition studies. Multiple human P‐450 enzymes (CYP3A4, CYPlA2, CYP2A6, and CYP2D6) catalyzed the sulfoxidation of DDTC‐Me, as determined with cDNA‐expressed enzymes. Several lines of evidence suggest that the sulfoxidation of DDTC‐Me by human liver microsomes is primarily catalyzed by CYP3A4/5, including (1) a high correlation between DDTC‐Me sulfoxidation and testosterone 6β‐hydroxylation; (2) increased DDTC‐Me sulfoxidation in the presence of α‐naphthoflavone, an activator of CYP3A enzymes; (3) inhibition of this reaction by inhibitors of CYP3A4/5 enzymes, such as troleandomycin and ketoconazole; and (4) inhibition of DDTC‐Mesulfoxidation by antibodies against CYP3A enzymes. On the other hand, several lines of evidence suggested that the thiono‐oxidation of DDTC‐Me by human liver microsomes is catalyzed in part by CYPlA2, CYP266, CYPPEl, and CYP3A4/5, including (1) these human P450 enzymes among others have the capacity to catalyze this reaction, as determined with cDNA‐expressed enzymes; (2) a high correlation between DDTC‐Me thiono‐oxidation and testosterone 6β‐hydroxylation, weak inhibition by ketoconazole, troleandomycin, and anti‐CYP3A antibodies suggested a minor role for CYP3A4; (3) a high correlation with immunoreactive CYP2B6 suggested involvement of this enzyme; (4) weak inhibition of DDTC‐Me thiono‐oxidation by furafylline and anti‐CYPlA antibody suggested involvement of CYPlA2, and (5) inhibition of DDTC‐Me thiono‐oxidation by DDTC and anti‐CYP2E antibodies suggested a role for CYP2E1. Collectively, these data suggested CYP3A4/5 enzymes are the major contributors to the sulfoxidation of DDTC‐Me by human liver microsomes, and CYPlA2, CYP2B6, CYP2E1, and CYP3A4/5 contribute toward DDTC‐Me thiono‐oxidation by human liver microsomes. This study, in conjunction with others (Madan et al., Drug Metab. Dispos. 23:1153–1162, 1995), may help explain the variability in disulfiram's effectiveness as an alcohol deterrent.
Matching Alcoholism Treatments to Client Heterogeneity: Project MATCH Three‐Year Drinking Outcomes
Authors:   Project MATCH Research Group
Published: May 2006

This study reports 3‐year outcomes for clients who had been treated in the five outpatient sites of Project MATCH, a multisite clinical trial designed to test a priori client treatment matching hypotheses. The main purpose of this study was to characterize the status of the matching hypotheses at the 3‐year follow‐up. This entailed investigating which matching findings were sustained or even strengthened across the 3‐year study period, and whether any hypotheses that were not supported earlier eventually emerged at 3 years, or conversely, whether matching findings discerned earlier dissipated at this later time. This research also examines the prognostic effects of the client matching attributes, characterizes the overall outcomes at 37 to 39 months, and explores differential effects of the three treatments at extended follow‐up. With regard to the matching effects, client anger demonstrated the most consistent interaction in the trial, with significant matching effects evident at both the 1‐year and 3‐year follow‐ups. As predicted, clients high in anger fared better in Motivational Enhancement Therapy (MET) than in the other two MATCH treatments: Cognitive‐Behavioral Therapy (CBT) and Twelve‐Step Facilitation (TSF). Among subjects in the highest third of the anger variable, clients treated in MET had on average 76.4% abstinent days, whereas their counterparts in the other two treatments (CBT and TSF) had on average 66% abstinent days. Conversely, clients low in anger performed better after treatment in CBT and TSF than in MET. Significant matching effects for the support for drinking variable emerged in the 3‐year outcome analysis, such that clients whose social networks were more supportive of drinking derived greater benefit from TSF treatment than from MET. Among subjects in the highest third of the support for drinking variable, TSF participants were abstinent 16.1 % more days than MET participants. At the lower end of this variable, difference in percent days abstinent between MET and TSF was 3%, with MET clients having more abstinent days. A significant matching effect for psychiatric severity that appeared in the first year posttreatment was not observed after 3 years. Of the 21 client attributes used in testing the matching hypotheses, 11 had prognostic value at 3 years. Among these, readiness‐to‐change and self‐efficacy emerged as the strongest predictors of long‐term drinking outcome. With regard to the overall outcomes, the reductions in drinking that were observed in the first year after treatment were sustained over the 3‐year follow‐up period almost 30% of the subjects were totally abstinent in months 37 to 39, whereas those who did report drinking nevertheless remained abstinent an average of two‐thirds of the time. As in the 1‐year follow‐up, there were few differences among the three treatments, although TSF continued to show a possible slight advantage.
Predicting the Development of Late‐Life Late‐Onset Drinking Problems: A 7‐Year Prospective Study
Authors: Schutte Kathleen K. , Brennan Penny L. , Moos Rudolf H.
Published: May 2006

There has been little empirical study of risk factors for the development of late‐life late‐onset drinking problems. In the current prospective study, we compare two groups of older adults who, at a baseline assessment, were nonproblem drinkers: individuals who developed drinking problems over the course of the next 7 years (n= 77) and those who did not (n= 197). Late‐onset problem drinkers reported mild to moderate drinking problems and spontaneous remission rates were high. Compared with stable nonproblem drinkers, late‐onset problem drinkers at baseline were more likely to report incipient problems, heavier alcohol consumption, greater friend approval of drinking, more reliance on avoidance coping strategies, were more likely to smoke, and were less likely to have acute medical conditions that could potentially be complicated by alcohol consumption. Contrary to expectation, life stressors did not predict drinking problem onset. However, compared with stable nonproblem drinkers, late‐onset problem drinkers were more likely to have a history of responding to stressors and negative affect with increased alcohol consumption.
Effect of Recent Alcohol Intake on Parathyroid Hormone and Mineral Metabolism in Men
Authors: Perry Horace M. , Horowitz Michael , Fleming Shantiel , Kaiser Fran E. , Patrick Ping , Morley John E. , Cushman William , Bingham Stephen , Perry H. M.
Published: May 2006

The mechanisms by which alcohol intake, particularly moderate alcoho1 intake, effects bone metabolism are poorly defined. We have examined the relationship between mineral metabolism and recent self‐reported alcohol intake (SRAI) across a wide range of such intakes in a series of 104 men aged 32 to 78 years of age in an outpatient setting. A morning nonfasting urine, serum specimen and recent SRAI were obtained from each subject. SRAI was reported as between 0 and 45 oz/week. SRAI correlated positively with her function tests, including serum bilirubin (r= 0.30, p= 0.002), alkaline phosphatase (r= 0.30, p= 0.004), and aspartate aminotransferase (SGOT) (r= 0.29, p= 0.006). SRAI correlated with serum calcium corrected for albumin (r= ‐0.39, p < 0.001), estradiol (r= 0.43, p < 0.001), and immunoreactive parathyroid hormone (iPTH) (r= ‐0.51, p < 0.001), as well as urinary calcium (per 100 mg of creatinine) (r= 0.55, p < 0.001). We have arbitrarily divided the participants into two groups on the basis of their reported alcohol intake. Individuals in the first group had intakes ranging from none to moderate intake (drank 8.4 oz or less of ethanol per week, equivalent to an average of two drinks daily or less). Those in the second group had moderate or heavier intake, with >8.4 oz of ethanol intake/week. Mean serum iPTH was significantly greater in those in the first group (none to moderate), compared with the second group (moderate or heavier) (56.0 ± 3.4 and 39.9 ± 2.0 pM/liter, respectively). Calcium corrected for serum albumin was significantly greater in individuals in the first, compared with the second, group (9.23 ± 0.05 vs. 8.88 ± 0.07 mg/dl, respectively). In addition, urinary calcium (cod per 100 mg of creatinine) was significantly lower in the former, compared with the latter (3.1 ± 0.4 vs. 8.4 ± 1.1 mg/100 mg of creatinine, respectively). Similarly, urinary excretion of collagen crosslinks (corrected per 100 mg of creatinine) was significantly less in men in the second group, compared with the first group (316 ± 38 vs. 530 ± 78 nM/100 mg of creatinine, respectively). Not surprisingly, a series of correlations between iPTH and age, 250‐hydroxyvitamin D, and testosterone were significant in individuals with none to moderate SRAI, but not moderate or heavier SRAI. Significant independent predictors of serum iPTH in the entire group of men were age (β= 0.215, p= 0.025), SRAI (β= ‐0.281, p= 0.003), 250‐hydroxyvitamin D (β= ‐0.309, p= 0.002), and testosterone (β=−184, p= 0.048). We have concluded that, in free‐living men, alcohol intake >8.4 oz/week was associated with decreased serum iPTH concentrations.
Screening for Alcoholism Among Medical Inpatients: How Important Is Corroboration of Patient Self‐Report?
Authors: Chermack Stephen T. , Singer Kathleen , Beresford Thomas P.
Published: May 2006

Little Is known about the utility of collateral reports in substantiating self‐report for individuals assessed in nonalcoholism treatment contexts. This study examined the concordance of 581 pairs of medical patient and collateral responses to a commonly used alcohol screening instrument, the CAGE Questions, as well as to reports of the patient's drinking consequences and alcohol consumption. Results demonstrated that patient/collateral concordance was marginal, but acceptable, on CAGE cut‐off scores and, that similar to reports from alcoholism treatment settings, patients generally reported more drinking consequences than collaterals. Patient and collateral reports of the patient's alcohol consumption did not differ significantly. This pattern of patient and collateral reporting of alcohol consequences and consumption was found for both men and women, as well as for patients with a DSM‐III‐R diagnosis of alcohol dependence. The findings support the validity of patient self‐report on alcoholism screening measures in medical settings. Furthermore, results demonstrated that the addition of collateral reports to information directly obtained from patients only modestly improved the Identification of alcohol dependence. The overall findings indicate that alcohol screening can be done effectively and efficiently in medical settings.
Development of a Questionnaire Method to Discriminate Between Typical and Atypical Genotypes of Low Km Aldehyde Dehydrogenase in a Japanese Population
Authors: Takeshita Tatsuya , Morimoto Kanehisa
Published: May 2006

Nearly half of all Orientals exhibit aversive symptoms, such as “Oriental flushing” or palpitation, during alcohol consumption. This high alcohol sensitivity among Orientals has been attributed to a highly prevalent polymorphism in low Km aldehyde dehydrogenase (ALDH2). In the present study, we attempted to develop a reliable questionnaire method to probe the frequency of alcohol drinking‐related symptoms to estimate the ALDH2 genotype. Four‐hundred twenty‐four male and 100 female workers provided blood samples for polymerase chain reaction analysis and completed the questionnaire. We performed a stepwise logistic regression analysis to discriminate between the typical homozygote (ALDH2*1/*1) and the atypical heterozygote (ALDH2*1/*2) in male subjects. Because of the limitation in the sample size for ALDH2*2/*2, this genotype was not included in the analysis. Results revealed that only three symptoms (facial flushing, flushing elsewhere, and palpitation) were enough to correctly predict the ALDH2 genotypes in ∼89% of all subjects. The present questionnaire method (ALcohol Sensitivity screening Test; ALST) takes a little time and effort for the genotype determination, and may be especially useful in epidemiological studies with a large sample size or with subjects from whom DNA samples are not available.
Estrous Cycle Effects on Operant Responding for Ethanol in Female Rats
Authors: Roberts A. J. , Smith A. D. , Weiss F. , Rivier C. , Koob G. F.
Published: May 2006

Human females have been reported to be uniquely sensitive to the deleterious effects of ethanol, thus it is important to study the characteristics of and mechanisms underlying alcohol consumption that may be specific to females. Models of ethanol self‐administration in female rats that take into consideration the estrous cycle have the potential to provide important information concerning these characteristics and mechanisms. The purpose of this study was to explore the effect of the cycle on ethanol self‐administration using a limited access operant paradigm. Female Wistar rats were trained to lever press for 10% ethanol versus water using a saccharin fading procedure. Responses were examined across the four phases of the estrous cycle. No effects of estrous cycle phase were observed when these rats were allowed to cycle freely. Subsequently, estrous phase effects were investigated in females whose cycles had been synchronized. Under this condition, an effect of estrous phase was present, with lower ethanol intake observed in estrus (and in some cases proestrus). Synchronized rats all showed at least one very clear 4‐day estrous cycle, whereas free‐running rats' cycles ranged from 3 to 5 days. Thus, it is more likely that synchronized rats were tested in the identical portion of each phase, when hormone levels were less variable. These results suggest that ethanol may be more reinforcing during diestrus than proestrus and estrus in female rats.
Phosphatidylethanol in Blood as a Marker of Ethanol Consumption in Healthy Volunteers: Comparison with Other Markers
Authors: Varga Arthur , Hansson Per , Lundqvist Christofer , Alling Christer
Published: May 2006

Phosphatidylethanol is a “pathological” phospholipid, formed via the action of phospholipase D only in the presence of ethanol. The present study was made to elucidate how different levels and patterns of alcohol intake affect blood levels of phosphatidylethanol in comparison with other markers of abuse. We used a new HPLC‐evaporative light‐scattering detection technique for phosphatidylethanol quantitation. This method had a total coefficient of variation of < 20% at the detection limit of 0.2 nmol, equaling 0.8 μmol/liter of whole blood. Two groups were studied. (a) Five healthy volunteers were given 32 to 47 g of ethanol in a single dose, to give blood ethanol levels of ∼25 mmol/liter after 30 to 60 min. Phosphatidylethanol, carbohydrate‐deficient transferrin (CDT), and blood ethanol were measured before and after the intake. (b) Twelve student volunteers were studied during a 3 week period of prolonged alcohol consumption (total estimated intake: 1334 ± 488 g, mean ± SD) and phosphatidylethanol, serum‐CDT, γ‐glutamyltransferase, and blood ethanol were measured at the start of the period (day 1) and twice at the end of the period (days 18 and 21). In group (a), no phosphatidylethanol was detected at any time after ethanol dosage/take. In group (b), no blood phosphatidylethanol or blood ethanol could be demonstrated at the start, and serum‐CDT was below the discrimination limit (1.3%) in all persons. No phosphatidylethanol was detected in those four persons with the lowest intake (742 ± 150 g). However, the remaining eight persons had detectable levels of phosphatidylethanol (1.0 to 2.1 μmol/liter), and these had a higher total intake (1630 ± 389 g). There was a statistically significant (p= 0.02) increase in serum CDT for 3 weeks. However, only 3 of 12 persons increased above the discrimination limit. The present results indicate that a substantial alcohol intake is needed to elevate blood phosphatidylethanol. In comparison with serum‐CDT, blood phosphatidylethano1 appears more sensitive.
Do Young Children of Alcoholics Hold More Positive or Negative Alcohol‐Related Expectancies Than Controls?
Authors: Wiers Reinout W. , Gunning W. Boudewijn , Sergeant Joseph A.
Published: May 2006

Alcohol‐related expectancies and alcohol use were examined in 185 children of alcoholics (COAs) and controls, aged 7 to 18 years. Concerning the expectancies of young COAs, two contrasting hypotheses have been proposed: COAs should hold more negative expectancies than controls due to aversive learning, or hold more positive expectancies due to either social learning or a more favorable response to alcohol. We propose that COAs of elementary school age hold more negative expectancies due to aversive learning, whereas older COAs hold more positive expectancies due to a more favorable response to alcohol. The critical variable with respect to the change from more negative to more positive expectancies is proposed to be the child's own initiation of alcohol use. The results of the present cross‐sectional study provide suggestive evidence in favor of this hypothesis. First, elementary school‐aged COAs had stronger negative expectancies than controls. Second, the hypothesized interaction between family history and own experience with alcohol was confirmed in the adolescent subsample. The proposed model should be critically tested with longitudinal data. If confirmed, the model may be of importance for prevention of alcohol‐related problems in high‐risk populations.
Alcohol Decreases T‐Lymphocyte Migration into Lung Tissue in Response to Pneumocystis carinii and Depletes T‐Lymphocyte Numbers in the Spleens of Mice
Authors: Shellito Judd E. , Olariu Ruxandra
Published: May 2006

Previous work from our laboratory has shown that chronic alcohol consumption in mice creates immunosuppression sufficient to permit infection with the opportunistic pathogen Pneumocystis carinii. Host defense against P. carinii is critically dependent upon host T lymphocytes. In these experiments, we address the effect of chronic alcohol consumption on recruitment of T lymphocytes into infected lung tissue and on lymphocytes in host lymphoid tissue. We find that mice administered alcohol in drinking water and then inoculated with P. carinii show significantly decreased recruitment of CD4+ and CD8+ T lymphocytes into lung tissue in comparison with control mice. Additional experiments show significant depletion of CD4+ lymphocytes in spleens from alcohol mice and decreased numbers of activated T lymphocytes. Analysis of surface expression of the adhesion molecules LFA‐1, VLA‐4, and CAM‐1 show no significant differences in lymphocytes from alcohol‐consuming mice, and lymphocyte chemotaxis in vitro is also unaltered. We conclude that chronic consumption of alcohol impairs lung recruitment of lymphocytes in response to an infectious challenge. This impaired lymphocyte recruitment may be a consequence of depletion of T lymphocytes in host lymphoid tissue. Impaired recruitment of lymphocytes may explain the increased morbidity and mortality of pulmonary infections in alcoholic subjects.
Decreased Sensitivity to the Hypnotic Effects of Ethanol Early in Ontogeny
Authors: Silveri Marisa M. , Spear Linda Patia
Published: May 2006

Sensitivity to the hypnotic effects of ethanol was examined in Sprague‐Dawley male and female rats at 16, 26, 36, 46, 56, or 96 days postnatally. Following administration of 3.5, 4.0, 4.5, or 5.0 g/kg of a 17% v/v ethanol solution, sleep times were recorded and blood alcohol levels (BALs) and brain alcohol levels (BrALs) were measured upon awakening. In addition to examining ethanol sleep time during ontogeny, data were used to estimate acute tolerance (indexed by the slope of the linear regressions of waking BALs and BrALs as a function of dose) and initial brain sensitivity to ethanol (indexed by calculating the y‐intercept from the linear regression of BrALs as a function of sleep time). The results showed a marked increase in sensitivity to ethanol hypnosis during ontogeny, with young animals exhibiting shorter ethanol‐induced sleep times and high waking BALs and BrALs. This ontogenetic increase in ethanol sensitivity was associated with a developmental decline in acute tolerance, with acute tolerance being most pronounced at postnatal day (P) 16 and evident only up to P36. Initial sensitivity conversely increased with age, with P16 pups showing lower initial brain sensitivity to ethanol than at all other ages. Gender differences emerged in adulthood, with males sleeping significantly longer than females at P56 and P96. These findings suggest that the marked insensitivity of young animals to the hypnotic effects of ethanol is related to both pronounced acute tolerance, as well as reduced initial brain sensitivity to ethanol early in life.
Release and Accumulation of Neurotransmitters in the Rat Brain: Acute Effects of Ethanol In Vitro and Effects of Long‐Term Voluntary Ethanol Intake
Authors: Darstein Melanie , Albrecht Clemens , López‐Francos Luis , Knörle Rainer , Hölter Sabine M. , Spanagel Rainer , Feuerstein Thomas J.
Published: May 2006

Release from and accumulation in tissue slices of some neurotransmitters under acute ethanol in naive rats and in long‐term voluntarily ethanol drinking rats were investigated. Slices of the rat caudatoputamen were prelabeled with [3H]choline and release of [3H]acetylcholine was stimulated through either N‐methyl‐d‐aspartate (NMDA) receptors or strychnine‐sensitive glycine receptors. Ethanol in vitro at 2%, 4%, and 6% (34 mM, 68 mM, and 102 mM, respectively) concentration‐dependently depressed the maximum effect of the concentration‐response curve of NMDA in naive rats. In contrast, voluntary ethanol consumption over months led to a significantly enhanced NMDA receptor response characterized by an increase in the maximum effect of the concentration‐response curve. The glycine receptor‐mediated release of [3H]acetylcholine, which is inhibited by acute ethanol in a competitive‐like fashion, was not changed in animals that ingested ethanol over months. Electrically evoked release of [3H]noradrenaline ([3H]NA) and its presynaptic modulation by morphine through μ‐opioid receptors in neocortical slices of the rat, preloaded with [3H]NA, was nearly identical in both ethanol‐naive rats and in ethanol drinking rats. The accumulation of [3H]γ‐aminobutyric acid in rat cerebellum tissue was neither affected by acute ethanol in vitro nor after chronic ethanol consumption. In summary, long‐term voluntary ethanol intake caused a significant increase in NMDA receptor function in the rat caudatoputamen, but did not result in changes in glycine‐evoked [3H]acetylcholine release of electrically evoked [3H]NA release modulated by morphine or cerebellar [3H]γ‐aminobutyric acid accumulation.
Measuring Lifetime Drinking Histories
Authors: Lemmens Paul H.
Published: May 2006

This paper is based on the session “Measuring Lifetime Drinking Histories” that was held on Tuesday May 13,1997 at the International Workshop on Consumption Measures and Models for Use in Policy Development and Evaluation. The session chair was Paul Lemmens; presenters were Marcia Russell, Ronald Knibbe, and Paul Lemmens; and panel discussants were Robin Room, John Searles, Linda Sobell, and Richard Wilsnack.
An Overview of Health Risks and Benefits of Alcohol Consumption
Authors: Thakker Kerstin Damström
Published: May 2006

This article provides an overview of the most recent evidence on health risks and benefits of alcohol consumption. Not only different types of dose‐response curves but also other factors are important to consider when balancing health risks and benefits of alcohol consumption. The association between alcohol exposure and the risk of developing alcohol‐related harm is multifactorial; there is a considerable individual variation in risk and a particular female susceptibility. Guidelines on drinking published over the last decade have become successively more restrictive. Whereas guidelines in the 19809 referred to “sensible drinking” or “responsible drinking,” more recent guidelines refer to “low‐risk drinking.” For an increasing number of groups, the recommendation is to avoid alcohol entirely. The need to consider individual risk factors and specific risk situations is increasingly emphasized. The possible net beneficial health effects of moderate drinking may be achieved in less risky ways by refraining from smoking, eating less dietary fat, and doing regular exercise. A number of health risks of moderate drinking have been demonstrated. Yet, for the moderate drinker, various psychosocial problems— especially in the area of productivity and relations—are more likely to develop than organ damage. Also, the risks involved in giving general guidelines on drinking have been widely discussed. If these guidelines were generally accepted and followed, it could have negative consequences on public health.