bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal Alcohol Exposure Alters Behavioral Laterality of Adult Offspring in Rats
Authors: PhD Betty Zimmerberg , Riley Edward P.
Published: April 2006

The effects of prenatal exposure to ethanol on side preference behavior were examined in adult Long Evens rats from three prenatal treatment groups: prenatal alcohol exposed (35% ethanol‐derived calories 35% EDC), nutritional control (0% ethanol‐derived calories, 0% EDC) or standard control (lab chow, LC). Rats prenatally exposed to alcohol exhibited less aide preference in a two‐lever operant dumber while responding for food reward and alternated between the left and right levers more than either control group, which did not differ from each other. Although side preference increased over days of testing in the control groups, the 35% EDC subjects' side preference did not change with increased experience. When responding on a nonrewarded schedule (extinction), the three prenatal treatment groups did not differ in side preference. Alcohol‐exposed offspring also displayed a marked difference in paw use compared to control subjects: while most of the control subjects used one paw preferentially, 35% EDC subjects used both paws together or alternated paws. Prenatal alcohol exposure appears to alter the normal development of behavioral laterality, and this altered development persists into adulthood. Prenatal alcohol exposure may also alter the functional Interaction between intrinsic laterality and reward contingencies.
Cardiac Mitochondrial Abnormalities in a Mouse Model of the Fetal Alcohol Syndrome
Authors: Nyquist‐Battie Cynthia , Freter Mark
Published: April 2006

Mitochondrial enzymes and respiration were studied in the hearts of mice exposed to ethanol in utero from gestational Day 8 to parturition. This treatment had previously been shown by electron microscopy to result in myofibril loss and mitochondrial abnormalities. Ethanol was administered to pregnant mice by a liquid diet paradigm and pair‐fed dams were used as controls. Ethanol exposure in utero reduced the activities of two mitochondrial inner membrane enzymes, cytochrome c oxidase and succinate dehydrogenase, in the hearts of perinatal mice. Secondly, mitochondrial respiration under both State 3 and 4 conditions with a NAD‐linked substrate was depressed in the hearts obtained from the ethanol‐exposed fetal mice. However, when a flavin‐linked substrate was used, State 3 (ADP‐stimulated) but not State 4 respiration was depressed. This study illustrates that in utero exposure to ethanol is deleterious to the functioning of cardiac mitochondria in newborn mice, which in turn could contribute to the development of the heart pathologies resent in the Fetal Alcohol Syndrome.
Interaction between Marihuana and Ethanol: Effects on Psychomotor Performance
Authors: Perez‐Reyes Mario , Hicks Robert E. , Bumberry Jean , Robert Jeffcoat A. , Cook C. Edgar
Published: April 2006

This is a report of the results of a placebo‐controlled study in which the effects of the interaction between ethanol and marihuana on drug plasma concentrations, subjective ratings of intoxication, heart rate acceleration, and psychomotor performance were investigated. Six healthy, male, paid volunteers, moderate users of ethanol and marihuana, participated in the study. Ethanol (0.42 g/kg, 0.85 g/kg, or placebo) was administered over a 30‐min interval. Fifteen minutes later the subjects smoked, in their customary manner, NIDA cigarettes containing 2.4% or 0.0004% (placebo) δ‐9‐etrahydrocannabinol (THC). Each subject was tested in a single‐blind, latin‐square crossover design with the following six conditions: placebo ethanol/placebo marihuana; low dose ethanol/placebo marihuana; high dose ethanol/placebo marihuana; placebo ethanol/marihuana; low dose ethanol/marihuana; and high dose ethanol/marihuana. The variables measured in the study were: (a) subjective rating of ethanol and/or marihuana intoxication; (b) heart rate; (c) accuracy and latency of response in the Simulator Evaluation of Drug Impairment (SEDI) task; (d) blood ethanol concentration by gas chromatography; and (e) plasma concentration of THC by radioimmunoassay. The results indicate that the decrements due to ethanol in performance of skills necessary to drive an automobile were significantly enhanced by marihuana in an additive and perhaps synergistic manner. The administration of ethanol prior to marihuana smoking did not produce significant effects on the subjective rating of “high”, heart rate acceleration, or THC plasma concentration.
Dose‐Additive Inhibition of Intake of Ethanol by Cholecystokinin and Bombesin
Authors: Kulkosky Paul J. , Glazner Gordon W.
Published: April 2006

Cholecystokinin (CCK) and bombesin (BBS) are neuropeptides of the brain and gut which have been shown to inhibit intake of ethanol. CCK octapeptide and BBS tetradecapeptide were injected intrapritoneally in both single doses and combinations of doses to determine Interactions of the two peptides in the control of consumption of ethanol. Water‐deprived rats were given access to 5% w/v ethanol for 30 min, followed by a 30‐min access to water, daily. One minute before presentation of ethanol, rats were injected with either saline or one of ten peptide solutions (three of CCK alone, three of BBS done, and four combinations of both). Results from the injections of single peptides were used to determine predicted inhibitions of the peptide combinations, assuming perfect additivity of doses. None of the actual values of inhibition of intake of ethanol by peptide combinations differed significantly from its predicted additive value. Endogenous CCK‐like and BBS‐like peptides may suppress intake of ethanol by an additive mechanism of inhibition.
Alterations in Regional Catecholamine Content and Turnover in the Male Rat Brain in Response to in Utero Ethanol Exposure
Authors: Dewey Cooper J. , Kevin Rudeen P.
Published: April 2006

Fetal ethanol exposure is known to produce CNS abnormalities. The molecular basis for these manifestations observed in animals exposed to ethanol in utero may be explained by changes in regional catecholamine content and turnover. This study was designed to determine changes in catecholamine content and turnover in the cerebral cortex, cerebellum, medial basal hypothalamus, diencephalon, and septal area of male rats exposed to ethanol pre‐ and postnatally. Pregnant Sprague‐Dawley rats were exposed to either an ad libitum liquid diet containing 35% ethanol‐derived calories, an isocalorically matched liquid diet, or a diet consisting of laboratory chow and water. Regional alterations in catecholamine content and turnover in each of the brain areas were observed on postnatal Day 18. A regional variability was demonstrated in the effect of in utero ethanol exposure on catecholamine content and turnover. The most dramatic effect was found in the dopaminergic neurons of the medial basal hypothalamus where in utero ethanol exposed offspring had a significantly reduced DA content and turnover when compared to pups from both isocalorically matched and chow‐fed dams. These data indicate that the dopaminergic neurons of this particular brain region are susceptible to alteration by ethanol exposure during development and that this alteration cannot be explained by changes in nutrition alone.
Long‐Term Alcohol Consumption Reduces the Number of Neuronal Nuclear Pores. A Morphometric Study Undertaken in CA3 Hippocampal Pyramids of Rats
Authors: Andrade J. P. , Cadete‐Leite A. , Paula‐Barbosa M. M. , Volk B. , Tavares M. A.
Published: April 2006

A close relationship between the number of nuclear pores and the cellular protein synthesis activity is known to exist. Previous biochemical Investigations lead to admit that the widespread neuronal alcohol‐induced degenerative changes could depend on a decrease in the neuronal protein synthesis. The morphometric analysis made on the nuclear pore complexes of CA3 hippocampal pyramids of long‐term alcohol‐fed rats fully supports this attractive hypothesis, since it has been found a marked reduction in the number of pores per unit surface area of nuclear membrane, together with a reduction in their total number per nucleus.
Altered Acylation of Erythrocyte Phospholipids in Alcoholism
Authors: Gastaldi Marguerite , Lerique Brice , Feugére Thérèse , Le Petit‐Thévenin Josette , Nobili Odette , Boyer Jean
Published: April 2006

The composition and metabolism of erythrocyte lipids were studied in 10 chronic alcoholic patients within 48 hr after discontinuation of alcohol intake and in 10 nonalcoholic control subjects. Chronic alcoholism produced no change in contents of cholesterol, total phospholipids, and proportions of phosphatidylcholine and phosphatidyl‐ethanolamine in erythrocyte phospholipids. The mean values of the rates of acylation of phosphatidylcholine and phosphatidylethanolamine with oleic acid were increased respectively by 59% (p < 0.001) and 38% (p < 0.05) as compared with the controls. There was no correlation between acylation rates and mean cellular volumes. Increases in acylation rates normalized over several weeks after alcohol withdrawal and were not related to a direct effect of alcohol on the intact erythrocyte, suggesting that these alterations result from ethanol‐induced changes in the membrane during erythrocyte formation. The increased rates of acylation might modify the remodeling of the lipid matrix and thereby the membrane function.
Alcohol Use and Depression Symptoms among Female Nursing Students
Authors: Haack Mary R. , Harford Thomas C. , Parker Douglas A.
Published: April 2006

A sample of 286 female nursing students responded to questions concerning drinking practices and symptoms of depression. After controlling for the possibly confounding effects of nursing student experiences (aspects of burnout such as depersonalization and social isolation) and the sociodemographic characteristics of the students, increased quantity of alcohol consumed per drinking occasion was found to be associated with increased symptoms of depression in the sober state.
Manipulation of Alcohol Preference in C57BL/6J Mice by Episodes of Food Poisoning
Authors: Ho Ann , Gentry R. Thomas , Chin Adrienne , Dole Vincent P.
Published: April 2006

Individual differences in the amount of alcohol consumed in a choice situation are found in highly inbred CS7BL/6J mice. The extent to which environmental stress can modify alcohol preference was studied by coupling acute episodes of poisoning with restricted fluid availability, and recovery with free choice of drinking fluids. Addition of actinomycin D, a mycotoxin, to ordinary chow during 2‐day periods produced acute episodes of nonlethal food poisoning from which the mice recovered rapidly. Consumption of a 10% alcohol solution and of water was recorded for several weeks before poisoning and for several weeks after the last episode. By varying drinking fluids available to the mice during the episodes of poisoning, long‐lasting changes in alcohol preference were produced. When 10% alcohol was the sole drinking fluid available during poisoning, preference for the alcohol solution was abolished. When water was the sole fluid during poisoning, alcohol preference was increased above the already high levels established in the baseline and above a control group that was restricted to water during the treatment periods bus was not poisoned. This increased alcohol preference was due to a nearly complete suppression of water intake in the posttreatment period; there was no significant increase in amount of alcohol consumed. The greatest individual differences in subsequent alcohol preference were found in the group of mice which continued to have free choice of alcohol and water during episodes of poisoning. The variety of responses to the same treatment show how environmental influences outside the experimenter's control may account for the variability found in voluntary alcohol consumption among genetically homogeneous mice.
Effects of Ethanol on Mature Offspring of Mice Given Ethanol during Pregnancy
Authors: Middaugh Lawrence D. , Ayers Kristina L.
Published: April 2006

Male offspring of mice maintained on isocaloric liquid diets containing either 20% ethanol or sucrose derived calories during pregnancy were tested on their ability to discriminate different ethanol doses as adults. They were trained to lever‐press for a food reward on each of two levers in an operant chamber, and were then maintained on an FR20 reinforcement schedule. After response rates stabilized, ethanol discrimination training was initiated by reinforcing only responses made on the drug appropriate‐lever after i.p. injections of ethanol (1.0 g/kg) or water. After learning to discriminate the 1.0 g dose, the animals' ability to discriminate doses of 0.25, 0.50, 0.75, 1.0, and 1.5 g/kg was assessed by determining the percentage of responses made on the drug lever during a 2‐min test period. Compared to sucrose controls, mice exposed to alcohol in utero learned the lever response more slowly and were less responsive to injected ethanol as evidenced by a reduced effect of the drug on response rates and by a reduction in their ability to discriminate the presence of injected ethanol. The results indicate that prenatal ethanol exposure can have long term consequences which reduce the effects of ethanol in fully mature animals.
Heavy Drinking and Regular Psychoactive Drug Use among Gynecological Outpatients
Authors: Russell Marcia , Coviello Donna
Published: April 2006

Self‐reported patterns of alcohol and drug use were examined in gynecological outpatients (n= 1967). Seventeen percent were heavy drinkers, 14% regularly used psychoactive drugs with the potential for nonmedical use, and over 3% both drank heavily and regularly used psychoactive drugs.

Significantly higher alcohol intakes (mean usual number of drinks per occasion was 3.6 compared to 3.1, p < 0.01) and more heavy drinkers (26% compared to 19%, based on quantity‐frequency, p < 0.01) were associated with regular psychoactive drug use. However, the relationship between other measures of alcohol use and regular psychoactive drug use varied as a function of age, marital status, and employment status.

Regular psychoactive drug use was significantly elevated among outpatients who were in their fifties, retired/other (not housewives, employed, or looking for work, e.g. students or disabled), not married, or white. The risk of regular psychoactive drug use was more than 1.5 times higher among heavy drinkers than among nonheavy drinkers.

It is estimated that there are over 35 million gynecologic office visits per year, therefore, increased case‐finding in this population has the potential to reach large numbers of women at risk who otherwise might not be identified.
Transferrin Phenotype and Level of Carbohydrate‐deficient Transferrin in Healthy Individuals
Authors: Stibler Helena , Borg Stefan , Beckman Gunhild
Published: April 2006

Elevated concentrations of carbohydrate‐deficient components of transferrin (CDT) in serum may be used as a sensitive and specific marker of regular, high alcohol consumption. When determined by a new, Simplified assay, CDT values are nearly normally distributed in low‐ or nonalcohol‐consuming control populations. The importance of transferrin phenotype for this normal variation was analyzed in 100 healthy, European men and women with no or negligible alcohol intake. No significant relation was found between phenotype and CDT value in this population. The three rare 6‐variants found had low CDT levels, and one subject, examined outside the study, with a rare D‐variant indicated that D‐variants may result in false‐positive CDT values. Moreover, women tended to have somewhat higher values than men, in whom CDT levels were weakly correlated with age. Other as yet undefined biological factors are clearly responsible for the major part of the normal variation of CDT values in nonalcoholic individuals.
Secular Trends in the Familial Transmission of Alcoholism
Authors: Reich Theodore , Cloninger C. Robert , Van Eerdewegh Paul , Rice John P. , Mullaney Joseph
Published: April 2006

This is a study of the familial transmission of alcoholism in the families of 60 female and 240 male alcoholics ascertained in four psychiatric hospital units and in a local parole office. Eight hundred and thirty‐one interviewed first‐degree relatives and 125 spouses are included. The lifetime population prevalences of alcoholism in white males and females based on the Epidemiological Catchment Area Study in St. Louis were compared with the family rates. A semistructured comprehensive interview schedule (Home Environment and Lifetime Psychiatric Evaluation Record) was used and diagnoses made according to Feighner criteria for alcoholism.

The methods of Survival Analysis established the presence of strong secular trends in the age‐of‐onset and lifetime prevalence of alcoholism in these families and in the general population. Accordingly, new methods for the analysis of family data that incorporate secular variation were developed.

The Multifactorial Model of Disease Transmission was used to estimate familial correlations and these were parameterized by the “Tau” model of Familial Transmission. The model does not assume that all familial resemblance is due to genetic factors, but also includes the possibility of nongenetic transmission. Our analyses confirmed that more recently born cohorts of individuals had increased expected lifetime prevalences of alcoholism and decreased ages of onset, when compared with older cohorts. Separate age‐of‐onset distributions were required for males and females and the secular trends in age‐of‐onset were greatest in females. The differences between males and females were least in more recently born cohorts suggesting that sex‐specific differences in the family and population distribution of alcoholism are decreasing.

Sex and cohort specific transmissibilities for alcoholism were found and the age‐specific transmissibilities in females (t2= 0.27–0.59) were significantly less than that for males (t2= 0.65–0.98). The transmissibilities were greatest in the youngest cohorts. The correlation between nonfamilial environmental factors common to siblings was 0.22 and a large degree of assortative mating was present (Rm=0.64).

The influence of parental transmissible factors was greater than that expected for polygenic transmission, strongly suggesting the presence of intrafamilial nongenetic familial transmission between generations.
Reactions to Alcohol in Sons of Alcoholics and Controls
Authors: Schuckit Marc A.
Published: April 2006

This paper synthesizes some major findings coming from our laboratory over the last decade. The data focuses on our search for mechanisms that might contribute to the elevated risk for alcoholism In sons of alcoholic fathers. Consistent results corroborated by several additional groups indicate that the higher risk sons of alcoholics demonstrate less intense reactions to ethanol as measured by their subjective self‐reports, measures of body sway, changes in several hormones after drinking, and the intensity or persistence of ethanol‐related changes on two electrophysiological measures. The potential implications of these results as they might relate to an enhanced vulnerability to alcoholism, and some possible future research directions, are discussed.
Childhood Personality Predicts Alcohol Abuse in Young Adults
Authors: Cloninger C. Robert , Sigvardsson Sören , Bohman Michael
Published: April 2006

431 children (233 boys, 198 girls) born in Stockholm, Sweden, had a detalled behavioral assessment at 11 years of age, including a detalled interview with their school teachers, and at age 27 years were reevaluated to identify alcoholism or alcohol abuse. Specific predictions from a neurobiological learning theory about the role of heritable personality traits in susceptibility to alcohol abuse were tested in this prospective longitudinal study. Three dimensions of childhood personality variation were identified and rated without knowledge of adult outcome. These three dimensions (novelty‐seeking, harm avoidance, and reward dependence) were largely uncorrelated with one another, and each was predictive of later alcohol abuse. Absolute deviations from the mean of each of the three personality dimensions were associated with an exponential increase in the risk of later alcohol abuse. High novelty‐seeking and low harm avoidance were most strongly predictive of early‐onset alcohol abuse. These two childhood variables alone distinguished boys who had nearly 20‐fold differences in their risk of alcohol abuse: the risk of alcohol abuse varied from 4 to 75% depending on childhood personality.
Underreporting of Alcohol Use in Pregnancy
Authors: Ernhart Claire B. , Morrow‐Tlucak Mary , Sokol Robert J. , Martier Susan
Published: April 2006

Studies of alcohol‐related birth defects in humans rely heavily on maternal self‐reports of alcohol use. The accuracy of self‐reports, and thus of related risk levels, is of concern to investigators, to public health professionals, and to persons advising pregnant women. We contrasted quantitative reports of drinking in pregnancy by 238 women with retrospective reports obtained 5 years later. Although correlated (r= 0.67, p <0.0001), marked discrepancies suggested underreporting during pregnancy by a significant proportion of the women. The validity of the retrospective index was indicated in that it was somewhat more highly related to scores on the Michigan Alcoholism Screening Test (MAST) and to a tally of alcohol‐related craniofacial anomalies in the neonate than was the in‐pregnancy index. Furthermore, the retrospective index and the MAST score were significant predictors of other neonatal anomaties; the in‐pregnancy index was not. The only variable related to underreporting was MAST score, i.e., the higher the MAST score the greater the underreporting. The results suggest that previously reported thresholds of effect based on self‐report data may be underestimates. The results also suggest that questions regarding alcohol‐related problems may be more effective than direct consumption questions in the identification of women who drink heavily in pregnancy.
Event‐related Potentials as Markers for Alcoholism Risk in High Density Families
Authors: Hill Shirley Y. , Steinhauer Stuart R. , Zubin Joseph , Baughman Timothy
Published: April 2006

One hundred sixty‐eight adult siblings and parents from affected and control families were tested for ERP characteristics using two tasks involving an auditory oddball paradigm. Significant within family differences among affected families suggest that risk for developing alcoholism may be seen even in adult subjects who have had experience consuming alcohol. Further, analysis of quantity and recency of drinking in the past seven days were not correlated with either amplitude or latency of Pa, suggesting that the within‐family differences observed reflect relative risk for developing alcoholism rather than experience with alcohol.
Ethanol‐induced Inhibition of Liver Cell Function: I. Effect of Ethanol on Hormone Stimulated Hepatocyte DNA Synthesis and the Role of Ethanol Metabolism
Authors: Carter Edward A. , Wands Jack R.
Published: April 2006

We have studied a short term effect (90 hr) of ethanol on hormone‐stimulated DNA synthesis in a primary rat hepatocyte culture system. Studies were also performed with respect to total RNA and protein synthesis as well as albumin secretion measured by a solid‐phase radioimmunoassay. We found that ethanol, when added to cultured hepatocytes, resulted in a substantial reduction in hormone‐stimulated hepatocyte DNA synthesis and this effect was concentration dependent and occurred in serum‐free medium. Ethanol also had an inhibitory effect on total RNA synthesis but protein synthesis and albumin secretion remained essentially unchanged. We determined that hepatocytes exposed to ethanol during the first 24 hr of culture were the most susceptible to inhibition of DNA synthesis. During the first 24 hr, alcohol dehydrogenase (ADH) activity was present in the cells at higher levels than at 48 and 72 hr. In human hepatoma cell lines and differentiated primary and secondary chick fibroblasts, no ADH activity was demonstrable; such cells were not inhibited by 100 mM ethanol additions and DNA synthesis rates were similar to untreated cultures. Other alcohols found to be metabolized by hepatocyte ADH were inhibitory towards hormone‐stimulated DNA synthesis whereas those with less metabolism had little effect. Hepatocytes treated with 4‐methylpyrazole, an inhibitor of ADH, were partially protected from ethanol effects. Taken together our results are consistant with the hypothesis that a major physiological effect of ethanol on the hepatocyte is a direct impairment of DNA synthesis and that alcohol metabolism is required.
A Nonhypoglycemic Chlorpropamide Analog that Inhibits Aldehyde Dehydrogenase
Authors: Nagasawa Herbert T. , Elberling James A. , Shirota Frances N. , DeMaster Eugene G.
Published: April 2006

Chlorpropamide (CP), a sulfonylurea‐type oral hypoglycemic agent, is known to provoke a flushing reaction reminiscent of the disulfiram‐ethanol reaction in certain individuals. This is manifested in rodents by an increase in blood acetaldehyde levels after ethanol administration. When the sulfonamide N1‐nitrogen of CP was substituted with an ethyl group, the product, N1‐ethylchlorpropamide, was found to be three times as active as CP in raising ethanol‐derived blood acetaldehyde. However, whereas CP lowered fasting blood glucose in rats measured over 6 h, N1‐ethylchlorpropamide was devoid of hypoglycemic activity, suggesting that the latter might be potentially useful as an alcohol deterrent agent.
Oral Ethanol Self‐administration in Rats: Models of Alcohol‐Seeking Behavior
Authors: Samson Herman H. , Pfeffer Anne O. , Tolliver Gerald A.
Published: April 2006

While various methods have been used to initiate ethanol drinking in animals, the development of models in which animals will perform some specific behavior in order to obtain the opportunity to drink ethanol has been fraught with difficulty. In the past several years, new procedures have been developed in which rats, neither food nor fluid deprived, will perform an operant task reinforced by the presentation of ethanol. This paper reviews some of these recent findings and presents new data concerning these models of oral ethanol self‐administration as measured in an operant paradigm.
Ethanol as a Reinforcer for Rats: Factors of Faciliation and Constraint
Authors: Stewart R. B. , Perlanski E. , Grupp L. A.
Published: April 2006

This review examines some particular approaches that have been used to investigate factors that facilitate or constrain the self‐administration of ethanol by rats. A technique for increasing ethanol self‐administration in rats, the prandial drinking method, was examined and the effect of body‐weight reduction on drug intake was discussed. Emphasis was placed on how ethanol intake may be controlled by processes in addition to the direct pharmacological actions of the drug in the CNS. These processes may be physiological. Evidence was presented for a relationship between activity in the renin‐angiotensin system and the self‐administration of ethanol. These processes may also be environmental. Using the place‐conditioning technique, demonstrations were presented of how the context or situation in which ethanol is experienced may determine whether preference or aversion for the drug develops. Such a diversity in the factors that can potentially control ethanol intake may complicate the identification of the causes of alcohol abuse, but this same diversity also holds out greater hope that manipulations may be found to reduce excessive drinking in humans.
Brain Stimulation Reward: Effects of Ethanol
Authors: Kornetsky Conan , Bain George T. , Unterwald Ellen M. , Lewis Michael J.
Published: April 2006

This paper briefly describes and compares the effects of ethanol with those of other abuse substances on brain stimulation reward. The most frequently observed effects of abuse substances on this phenomenon is an increase in sensitivity of the animal to the stimulation. This increased sensitivity to rewarding brain stimulation has been studied as a model of drug‐induced euphoria. Although many studies have reported that ethanol does increase the sensitivity of animals to this stimulation, there is much less consistency in results between laboratories than observed with the abused opiates or psychomotor stimulants. Data is presented that suggests that associative factors, e.g., self‐ versus experimenter‐administered ethanol, as well as route of administration and time of brain stimulation testing may all contribute to the variability in results obtained between laboratories. Further, the effects of ethanol on brain stimulation reward are more like those of other sedative‐hypnotics than the opiates or psychomotor stimulants.
Abstracting Deficits and Childhood Conduct Disorder as a Function of Familial Alcoholism
Authors: Schaeffer Kim W. , Parsons Oscar A. , Errico Austin L.
Published: April 2006

Using a large sample (n= 515), family history‐positive male alcoholics (FH+) performed poorer than family history‐negative (FH‐) alcoholics on a test of abstracting ability. They also reported an earlier age of onset of alcoholism, more symptoms of childhood conduct disorder, and tended to report more depressive symptoms than FH‐ alcoholics, however, these variables were not significantly related to abstracting score. FH+ and FH‐ samples did not differ on average amount of ethanol consumed per day, vocabulary, state anxiety, childhood attentional deficit disorder, and childhood learning disability. The significant differences found in this study between FH+ and FH‐ alcoholics were minimal. With such weak effects, the inconsistent findings in studies that have investigated differences between FH+ and FH‐ alcoholics are understandable.
Loss of Cholinergic Muscarinic Receptors in the Frontal Cortex of Alcohol Abusers
Authors: Freund Gerhard , Ballinger William E.
Published: April 2006

Alcohol abuse causes impairment of cognitive function ranging from mild forms to end‐stage dementia. Alcohol‐related dementia accounts for nearly 20% of all admissions to state mental hospitals and may result from head trauma, thiamine deficiency, Alzheimer's, and other brain diseases that can be diagnosed conclusively only at autopsy. However, we postulate that after all these conditions have been excluded, an “alcohol encephalopathy” remains. This is characterized by impaired synaptic function, which underlies the continuum of impaired intellectual function. We found in 79 histologically normal brains of a nondemented general hospital population a 40% decrease in the density of cholinergic muscarinic receptors in the frontal cortex of alcoholics when compared with matched controls of the same age. Only alcohol abuse and not aging, postmortem changes, medications, clinical (including liver) diseases, or differences in causes of death could account for this loss.
Effect of Acute Ethanol Administration on Human Blood Aldehyde Dehydrogenase Activity
Authors: Helander Anders , Tottmar Olof
Published: April 2006

The aldehyde dehydrogenase (EC 1.2.1.3) activity in human blood was measured after acute oral administration of two different doses of ethanol to healthy subjects. No changes in aldehyde dehydrogenase activity were observed in either of the two dose groups, as compared to control subjects receiving no ethanol. Likewise, incubation of human whole blood samples with 20 mM ethanol for 2 hr caused no change in aldehyde dehydrogenase activity. The results show that human blood aldehyde dehydrogenase activity is not affected by acute ethanol administration.
Ethanol‐induced Changes in Morphology and Strength of Femurs of Rats
Authors: Peng Tai‐Chan , Kusy Robert P. , Hirsch Philip F. , Hagaman John R.
Published: April 2006

Chronic ingestion of ethanol resulted in ultrastructural and mechanical changes in rat femurs. Scanning electron microscopy of the distal end of the femur revealed that the trabeculae of bones from ethanol‐fed rats were thinner, more columnar, and more extensive than those from control rats. Three‐point bending tests of the rat femurs showed that the maximum force or so‐called “strength” required to break the bone was less in ethanol‐ than in control‐fed animals. A significant inverse correlation was observed between the strength required to break the femur and the dose of ethanol calculated on a body weight basis.

For the first time our study presents quantitative proof that a relationship exists between bone strength and the consumption of ethanol in rats. The study revealed that ethanol consumption resulted in a weaker femur compared to controls. We suggest that a common mechanism may be responsible for the decreased bone strength of ethanol‐fed rats and the increased incidence of fractures in human alcoholics.
Specificity of Antibody Tests for Human Immunodeficiency Virus in Alcohol and Parenteral Drug Abusers with Chronic Liver Disease
Authors: Novick David M. , Des Jarlais Don C. , Jeanne Kreek Mary , Spira Thomas J. , Friedman Samuel R. , Gelb Alvin M. , Stenger Richard J. , Schable Charles A. , Kalyanaraman V. S.
Published: April 2006

Parenteral drug abusers are at risk for acquired immunodeficiency syndrome (AIDS), which is caused by human immunodeficiency virus (HIV). We tested stored sera for antibody to HIV (anti‐HIV) using two enzyme‐linked immunosorbent assay (ELISA) methods and Western blot. The patients were parenteral drug abusers who had undergone percutaneous liver biopsy for chronic liver disease. Current or former alcohol abuse was noted in 88 (80%) of the 110 patients. The sensitivities of the two ELISA tests in comparison with Western blot, the more specific test for HIV, were 100 and 94%, respectively; the specificities were 94 and 99%. Western blot was positive in 36 (33%) of 110 patients. False‐positive ELISA reactions for anti‐HIV were seen in five (7%) of 70 patients with negative Western blot analyses. Compared to true‐negatives, false‐positives had significantly more years of alcohol abuse, younger ages of onset of alcohol abuse, greater frequencies of jaundice and edema, higher levels of alkaline phosphatase, total billirubin, total protein, and globulins, and lower levels of serum albumin. In a stepwise logistic regression, only hyperglobulinemia was significantly associated with a false‐positive anti‐HIV. We conclude that: (a) ELISA tests for anti‐HIV are useful for screening abusers of alcohol and parenteral drugs with chronic liver disease for HIV infection, but positive results must be confirmed with more specific tests such as Western blot; (b) false‐positive ELISA reactions in this population are associated with hyperglobulinemia; and (c) studies of HIV testing are needed in other populations of patients with alcoholism or liver disease.
Area Postrema and Alcohol: Effects of Area Postrema Lesions on Ethanol Self‐Administration, Pharmacokinetics, and Ethanol‐induced Conditioned Taste Aversion
Authors: Stewart R. B. , Perlanski E. , Grupp L. A.
Published: April 2006

An investigation was carried out to test the hypothesis that the area postrema (AP) may detect ethanol as a blood‐borne toxin and thereby mediate aversive postingestinal effects of the drug. These aversive effects in turn may impose an upper limit on the amount of drug that can be consumed. In Experiment 1 rats had continuous access to water and a 4% ethanol solution. Animals with AP lesions drank more ethanol than sham‐operated controls. No differences in drug disposition or metabolism were found when these rats were injected with ethanol and blood ethanol levels were measured. If the AP lesions resulted in increased ethanol drinking because of a reduction in the aversive effects of the drug, then the lesions might also be expected to attenuate a conditioned taste aversion induced by ethanol. In Experiment 2, groups of lesioned and sham‐operated rats drank a novel tasting fluid and then were given i.p. injections of ethanol (0.9, 1.2, or 1.6 g/kg) or vehicle. Similar degrees of aversion to the taste of the fluid developed in both the lesioned and the sham‐control groups. Since the AP lesion did not result in the attenuation of the ethanol‐induced conditioned taste aversion, it was suggested that the AP may not mediate the aversive consequences of ethanol and that the increased ethanol self‐administration observed in Experiment 1 may be due to other effects of the lesion.
Purification and Characterization of Beef and Pig Liver Aldehyde Dehydrogenases
Authors: Guan Kurt Liang , Pak Youngmi Kim , Tu Guang Chou , Na Cao Qing , Weiner Henry
Published: April 2006

Beef liver cytosolic, mitochondrial, and pig liver mitochondrial aldehyde dehydrogenases (ALDH) had been purified to homogeneity. The two mitochondrial enzymes as with other mammalian mitochondrial enzymes had properties very similar to that of the corresponding human enzyme. These include immunological as well as basic kinetic properties such as low Km for aldehyde, activation by Mg2+ ions, and lack of inhibition by disulfiram. A major difference between these two enzymes and the human mitochondrial enzyme was that they contained an N‐terminal‐blocked amino acid. Cytosolic ALDHs from human and horse liver have been shown to possess an N‐acetyl serine as the N‐terminal residue; beef cytosolic ALDH was also found to be blocked. Tissue preparations and subcellular fractions from beef or pig liver could be used to study acetaldehyde oxidation. This is the subject of the accompanying paper (Cao Q‐N, Tu G‐C, Weiner H, Alcohol Clin Exp Res 12xxx‐xxx, 1988).
Teenage Alcohol Use in the Australian Twin Register: Genetic and Social Determinants of Starting to Drink
Authors: Heath A. C. , Martin N. G.
Published: April 2006

Retrospective information about teenage alcohol use was obtained from 1589 adult twin pairs aged 20–30 years from the Australian twin register. Twin pairs were highly concordant both for teenage drinking (or abstinence) and for early versus late onset of drinking. Sociodemographic variables (e.g., paternal occupation and parental religious affiliation) and psychosocial variables (e.g., personality and attitudinal traits), assessed when the twins were adults, were comparatively poor predictors of teenage drinking. Environmental influences on onset of drinking appeared to be sex‐specific, i.e., uncorrelated over twins from unlike‐sex pairs. Among drinkers, early versus late onset of drinking was more strongly influenced by inherited factors in females, but by shared features of the social environment (e.g., family background or school experience) in males.
Investigation of an Acetaldehyde‐Hemoglobin Adduct in Alcoholics
Authors: Stockham Teri L. , Blanke Robert V.
Published: April 2006

It has been proposed that an ethanol‐related adduct is formed with hemoglobin in chronic alcoholics. This proposal is based on the observation that alcoholics were found to have an elevation of minor hemoglobins but normal amounts of glycosylated hemoglobin (HbA1c). Since acetaldehyde is believed to be the primary candidate involved in adduct formation, investigation was focused on this particular compound. This study describes the attempt to isolate and purify an acetaldehyde‐hemoglobin adduct in alcoholics by cationexchange chromatography and m‐aminophenylboronic acid affinity chromatography for the purpose of characterization. Using acetaldehyde concentrations of 5 and 10 mM, an acetaldehyde adduct with hemoglobin was formed in vitro, isolated, and characterized. However, a similar adduct could not be isolated in vitro using a pharmacological concentration of 100 μM acetaldehyde nor could this adduct be isolated in human alcoholic subjects.
Oral Ethanol Self‐Administration in Free‐Feeding Rhesus Monkeys
Authors: Grant Kathleen A. , Johanson Chris Ellyn
Published: April 2006

The ability of a conditioning procedure to establish oral ethanol self‐administration in free‐feeding rhesus monkeys was assessed. The conditioning procedure required the monkey to drink an ethanol solution in order to have access to a sweet orange‐flavored solution. Following an average of 14 sessions under these conditions, the orange solution was no longer delivered and ethanol solution alone was made available in the sessions. During both the conditioning and the ethanol self‐administration portions of the experiment each monkey was required to drink an average of 0.5 g/kg ethanol per session in order to continue in the experiment. Of the nine monkeys exposed to these contingencies, five monkeys continued to self‐administer ethanol after the presentation of the orange drink was discontinued. However, two of these five monkeys decreased their ethanol solution intake below 0.5 g/kg within 3 weeks after the conditioning sessions had terminated. The three monkeys that sustained high ethanol intake were male and had histories of drug self‐administration, suggesting that gender and drug history may influence the initiation of ethanol self‐administration. Once ethanol self‐administration was established, concentrations of ethanol from 4 to 15% (v/v) were made available. The monkeys consumed intoxicating amounts of ethanol, as indicated by average intakes ranging from 0.5 to 0.9 g/kg and blood ethanol levels over 100 mg/dl. These results demonstrate that ethanol self‐administration can be established and maintained through the initial reinforcement of ethanol consumption by the contingent presentation of another reinforcing stimulus. However, the results of this study also indicate that individual differences may be an important determinant of animals initiating ethanol self‐administration.
Bedtime Ethanol Increases Resistance of Upper Airways and Produces Sleep Apneas in Asymptomatic Snorers
Authors: Mitler Merrill M. , Dawson Arthur , Henriksen Steven J. , Sobers Mark , Bloom Floyd E.
Published: April 2006

Nasal continuous positive airway pressure (nasal CPAP) and polysomnography were used to analyze the time course of the effect of bedtime ethanol on resistance of upper airways and on the number of respiratory pauses during sleep. On one night, six asymptomatic nonalcoholic male snorers drank 2 ml/kg of 100 proof vodka mixed in orange juice (ethanol dose, 0.79 gm/kg, giving a peak blood alcohol level of 71.8 ± 33.3 mg/dl). On a second night they received a placebo (1–2 drops of vodka floated on top of the orange juice). We measured (a) the minimum nasal CPAP required to eliminate snoring, (b) the number of hypopneas and apneas during each hour of sleep and (c) the arterial oxygen saturation (SaO2) by ear oximetry. On the alcohol night there was a significant increase in the CPAP pressure required to eliminate snoring (placebo 4.8 ± 1.7 cm H2O, alcohol 6.2 ± 1.5 cm H2O). The number of respiratory events per hour of sleep (apnea index) was 7.5 ± 2.1 for ethanol nights versus 3.8 ± 2.7 for placebo nights (p < 0.0125). An apnea index of greater than 5 is generally considered abnormal. There was no significant difference in the number of desaturation events (declines of 4% or more in the SaO2) or in the mean SaO2, but the minimum SaO2 was significantly lower on the ethanol night (placebo 89.8%± 1.6, alcohol 86.8%± 2.7, p < 0.05). The effect of this dose of alcohol on airway resistance was most pronounced during the first 2 hr after ingestion.
Diminished Insulin‐like Growth Factor‐1 Levels after Chronic Ethanol: Relationship to Pulsatile Growth Hormone Release
Authors: Sonntag William E. , Boyd Rhonda L.
Published: April 2006

Previous studies have clearly demonstrated a reduction in plasma levels of IGF‐1 in rats chronically fed an ethanol diet. The purpose of this study was to determine whether the reduction in IGF‐1 was associated with alterations in growth hormone secretory dynamics. Male Sprague‐Dawley rats were fed either a liquid diet containing 5% ethanol or an identical volume of diet made isocaloric with maltose‐dextrin (pair‐fed controls). After 4 months of continuous feeding, another group of animals of the same age was introduced into the colony and fed the maltose‐dextrin diet ad libitum. All animals were atrial cannulated 4.5 months after the initiation of the experiment and serial samples of blood removed at 20‐min intervals for periods up to 6 hr. Plasma was separated and growth hormone and IGF‐1 concentrations determined by radioimmunoassay. Growth hormone secretory dynamics were analyzed by Cluster Analysis. Our results demonstrated that (a) chronic ethanol administration decreases plasma IGF‐1 concentrations compared to either ad libitum or pair‐fed control animals, (b) a reduction in dietary intake of approximately 33% reduces both the number of detectable growth hormone pulses and nadir concentrations of this hormone but has no effect on peak height, peak width, or area under the peak, and (c) ethanol feeding increases the amplitude of growth hormone pulses compared to pair‐fed rats. We conclude that the decrease in plasma IGF‐1 levels in ethanol as compared to pair‐fed control animals is not caused by a further reduction in growth hormone secretory dynamics. Our results support the hypothesis that ethanol directly inhibits IGF‐1 secretion from the liver.
Low Dose Alcohol Contracts the Human Umbilical Artery in Vitro
Authors: Savoy‐Moore R. T. , Dombrowski M. P. , Cheng A. , Abel E. A. , Sokol R. J.
Published: April 2006

Beginning at very low concentrations (0.001 g/100 ml), alcohol elicited dose‐dependent contractions of the human umbilical artery in vitro. Additionally, 16 of the 108 arteries tested had a 5‐10‐min spasm in response to alcohol. Alcohol (0.2 91100 ml) also increased tension developed in response to all angiotensin II doses, but had no effect on serotonin‐induced contractions. These results suggest that alcohol may increase umbilicoplacental resistance in vivo, thus decreasing fetal‐placental blood flow.
Effect of Chronic Ethanol Administration on Protein Catabolism in Rat Liver
Authors: Donohue Terrence M. , Zetterrnan Rowen K. , Turna Dean J.
Published: April 2006

Hepatic protein catabolism was measured in rats which were pair‐fed a liquid diet containing either ethanol or isocaloric maltose‐dextrin (control diet). Within 12 days after initiation of pair feeding, the level of total hepatic protein in ethanol‐fed rats was 26K higher than that in pair‐fed control rats. During this time interval, the catabolic rates of both short‐lived [3H]puromycin‐labeled proteins and long‐lived native [14C]bicarbonate‐labeled proteins were measured In the two groups of animals. The degradation rate of short‐lived [3H] puromycinyl proteins and peptides was the same in ethanol‐fed and pair‐fed control rats. However, the overall catabolic rate of long‐lived proteins in rats fed the ethanol liquid diet for 2‐10 days was 37‐40% lower than that in pair‐fed controls. This difference in protein turnover was not a general phenomenon, since the time‐dependent decay of [14C]proteins in the hepatic microsome fraction of ethanol‐fed rats was 33% slower than that in pair‐fed controls, but the apparent rate of cytosolic protein catabolism was the same in both groups of animals. The differences in protein turnover did not reflect quantitative changes in lysosomal proteases since the activities of four hepatic lysosomal cathepsins were unaffected by alcohol administration. When rats were subjected to longer periods of pair feeding (16‐25 days), the difference in overall hepatic protein catabolism between ethanol‐fed rats and their pair‐fed controls was considerably attenuated. Our findings indicate that during the early stages of pair‐feeding, animals consuming ethanol showed a slower rate of degradation of long‐lived hepatic proteins compared with pair‐fed control rats. Since a significant determinant of cellular protein content is the rate of protein degradation, the results suggest that the lower rate of protein catabolism in ethanol‐fed rats accounts for part of the net hepatic protein accumulation in these animals.
Acetylation Phenotype in Abstinent Alcoholics
Authors: Guthrie Sally K. , Lane Elizabeth A. , Linnoila Markku
Published: April 2006

No association between acetylation phenotype and alcoholism was discovered. Fifty‐four percent of both the alcoholic patients and healthy volunteers were rapid acetylators. Acetylation phenotyping is not helpful to the investigation 01 the genetics of alcoholism.