bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethanol‐Induced c‐Fos Expression in Catecholamine‐ and Neuropeptide Y‐Producing Neurons in Rat Brainstem
Authors: Thiele Todd E. , Cubero Inmaculada , Van Dijk Gertjan , Mediavilla Cristina , Bernstein Ilene L.
Published: April 2006

Background: Previous studies have used c‐Fos‐like immunoreactivity (cFLI) to examine the neuroanatomical location of cells that are activated in response to ethanol administration. However, the use of cFLI alone fails to reveal the phenotypical identity of cells. In the present study we used double‐labeling procedures to identify the neurochemical phenotype of neurons that showed ethanol‐induced cFLI in the rat brainstem.

Methods: Individual groups of rats received intraperitoneal injection of ethanol (1.5 g/kg or 3.5 g/kg) or isotonic saline (23 ml/kg). To assess the specificity of cFLI induced by ethanol, we injected other rats with the drug lithium chloride (LiCl; 76 mg/kg). Two hours after injection, rats were killed and their brains were processed for immunohistochemistry.

Results: Both doses of ethanol promoted cFLI in several brainstem regions, including the nucleus of the solitary tract (NTS), the locus coeruleus (LC), and the ventrolateral medulla (VLM). Although LiCl caused significant cFLI in the NTS, this drug promoted only minimal cFLI in the VLM and no significant activation in the LC. We found that a significant proportion of tyrosine hydroxylase (TH)‐positive neurons coexpressed ethanol‐induced cFLI in the VLM (∼75–85%), the NTS (∼65–75%), and the LC (∼30–65%). Additionally, a significant proportion of neuropeptide Y (NPY)‐producing neurons in the VLM coexpressed ethanol‐induced cFLI (∼60–75%). On the other hand, LiCl promoted activation of TH‐positive neurons in the VLM and the NTS but failed to stimulate cFLI in TH‐producing neurons in the LC or in NPY‐producing neurons of the VLM.

Conclusions: Neurons in the rat brainstem that show ethanol‐induced c‐Fos expression produce catecholamines and NPY. This research demonstrates the usefulness of double‐labeling immunohistochemistry procedures for identifying the neurochemical identity of neurons that are activated after ethanol administration.
The Modulation of B16BL6 Melanoma Metastasis Is Not Directly Mediated by Cytolytic Activity of Natural Killer Cells in Alcohol‐Consuming Mice
Authors: Spitzer Jessica H. , Núñez Nomelí P. , Meadows Sarah A. , Gallucci Randle M. , Blank Sally E. , Meadows Gary G.
Published: April 2006

Background:Previous studies in our laboratory indicate that alcohol consumption suppresses the metastasis of B16BL6 melanoma, whereas the cytolytic activity of natural killer (NK) cells is decreased in female C57BL/6 mice given 20% w/v alcohol in their drinking water. In the present study, we further evaluated the involvement of NK cells and alcohol consumption in the cytolytic activity of NK cells, the surface expression of NK phenotypic markers, and metastasis of B16BL6 melanoma in C57BL/6 beige (bgJ/bgJ) mutant mice, which possess inherently low NK‐cell cytolytic activity.

Methods:Beige and control (bgJ/+) mice were given either water or 20% w/v of alcohol in drinking water for 61/2 to 7 weeks before assay for cytolytic activity, surface marker expression, and inoculation with B16BL6 melanoma intravenously or into the pinna of the ear.

Results:NK cytolytic activity was suppressed in beige mice, and alcohol consumption did not modulate further the cytolytic activity. Beige mice had a lower percentage of NK cells in the peripheral blood and spleen than control mice. Peripheral blood lymphocytes from beige mice also exhibited a reduced percentage of CD4+T lymphocytes. Alcohol consumption similarly reduced the percentages of NK1.1‐ and LGL‐1‐expressing lymphocytes in the peripheral blood and spleen and reduced the percentage of CD8+T lymphocytes in the peripheral blood in both control and beige mice. Tumor lung colonization was increased in beige mice relative to control mice after intravenous inoculation of B16BL6 melanoma. The increase was more pronounced in water‐drinking beige mice than in control mice irrespective of alcohol consumption. Tumor lung colonization was significantly decreased (p< 0.05) by alcohol consumption in one experiment and partially decreased (p= 0.07) in the other. Mice that were inoculated into the pinna of the ear also exhibited a blunted antimetastatic response to alcohol consumption.

Conclusions:These data suggest that the presence of the beige mutation diminishes the antimetastatic effect of alcohol consumption and that there is no interaction between alcohol consumption and NK‐cell activity in the modulation of lung metastasis of B16BL6 melanoma cells.
Brain High Energy Phosphate Responses to Alcohol Exposure in Neonatal Rats: An In Vivo 31P‐NMR Study
Authors: Cudd Timothy A. , Wasser Jeremy S. , Chen Wei‐Jung A. , West James R.
Published: April 2006

Background: The mechanisms that mediate fetal brain injury which results from maternal alcohol consumption are not well understood. Although fetal hypoxia is a popularly proposed mechanism, it has been difficult to assess brain oxygenation in vivo. We measured intracellular high energy phosphate concentrations and estimated intracellular pH (pHi) in brains of unanesthetized neonatal rat pups by using in vivo 31P‐NMR spectroscopy. We reasoned that decreases in brain oxygenation sufficient to result in brain injury would also reduce high energy phosphates and pHi.

Methods: On postnatal day 4, before alcohol administration, pups were placed into a 20 mm diameter NMR probe, their heads were positioned carefully in the center of the 31P detection coil, and spectra were collected over 20 min. Animals were then fed diet with or without 4.5 g/kg of ethanol in two (in succession) of 12 daily feedings via artificial rearing methods. A second spectrum was collected at 90 min after the beginning of the second alcohol feeding, at the time that coincided with the peak blood alcohol concentration (BAC). Identical feedings were performed daily until day 9, when pre‐ and postfeeding spectra were again obtained. Positive control groups were fed control diet and were studied in atmospheres of 5% oxygen, 95% nitrogen or 0% oxygen, 100% nitrogen.

Results: Phosphocreatine (PCr), β‐adenosine triphosphate (ATP), and pHi decreased and inorganic phosphate (Pi) increased in day 4 animals subjected to 0% oxygen (20 min) compared with pretreatment and all other treatment groups. Day 9 animals did not tolerate these conditions. There were no significant changes in response to 5% oxygen on day 4, but Pi increased and β‐ATP decreased compared with pretreatment values and compared with alcohol and control groups on day 9. There were no changes in PCr, β‐ATP, or pHi in response to alcohol treatment at either age. PCr was significantly increased in the alcohol and 5% oxygen groups and apparently increased in the control group on day 9 compared with day 4, most likely due to increases in cranial muscle mass within the NMR coil.

Conclusions: We conclude that acute alcohol exposure that results in peak BACs of 315 mg/dl does not alter brain high energy phosphate concentrations or pHi in neonatal rat pups, although these BACs are known to result in significant brain injury. These findings do not support hypoxia as a mechanism of alcohol‐mediated brain injury during the third trimester equivalent in the rat pup model.
Chronic Ethanol Administration Alters Immunoreactivity for GABAA Receptor Subunits in Rat Cortex in a Region‐Specific Manner
Authors: Grobin A. Chistina , Fritschy Jean‐Marc , Morrow A. Leslie
Published: April 2006

Background: Chronic ethanol administration has a plethora of physiological effects. Among the most consistently observed findings is a change in the expression pattern of γ‐aminobutyric acid type A (GABAA) receptor subunits in the rat brain cortex. These findings led to the hypothesis of “subunit substitution” to account for changes in receptor function without changes in receptor number.

Methods: We used subunit (α1 and α4) specific antibodies and a combination of immunohistochemistry and immunoblotting to examine subregions of cortex (prefrontal, cingulate, motor, parietal, and piriform) for their response to 2 weeks of forced ethanol administration.

Results: Overall, cortical immunoreactivity for the α1 subunit was decreased and for the α4 subunit increased whether measured immunohistochemically or by immunoblotting. Piriform cortex exhibited a bidirectional change in GABAA receptor α1 and α4 immunoreactivity, similar to that previously observed in preparations of whole cortex. However, in parietal cortex, declines in α1 immunoreactivity (55 ± 12% control value [CV] and 88.3 ± 4.3% CV; immunohistochemistry and immunoblotting, respectively) were not accompanied by concomitant increases in α4 immunoreactivity (104 ± 8% CV and 116 ± 9.3% CV; immunohistochemistry and immunoblotting, respectively). Conversely, α4 immunoreactivity increased in cingulate cortex (210 ± 30% CV and 134 ± 9.5% CV; immunohistochemistry and immunoblotting, respectively) without a decline in α1 immunoreactivity (90 ± 4% CV and 91.3 ± 3.9% CV; immunohistochemistry and immunoblotting, respectively). Prefrontal and motor cortex exhibited GABAA receptor subunit peptide alterations, but these changes varied with the method of analysis.

Conclusions: These findings demonstrate that ethanol dependence results in nonuniform changes in GABAA receptor subunit peptide levels across the rat brain cortex and suggest that mechanisms which subserve functional changes in receptor activity may vary in accordance with anatomic or cellular differences within the cortex.
Changes in Activity and Regulation of the Cardiac Ca2+ Channel (L‐Type) by Protein Kinase C in Chronic Alcohol‐Exposed Rats
Authors: Solem Michele , Almas John , Rubin Emanuel , Thomas Andrew
Published: April 2006

Background: It has been reported recently that long‐term alcohol exposure in rats increases the number of dihydropyridine binding sites in cardiac membrane preparations. We fed Sprague Dawley® rats a liquid diet that contained ethanol as 36% of total calories for 4 to 6 months and studied how alcohol exposure affected the activity and regulation of the cardiac Ca2+ channel.

Methods: Dihydropyridine‐sensitive cardiac Ca2+ channel activity was measured as the rate of Mn2+ quench of the cytosolic fura‐2 signal in electrically stimulated myocytes.

Results: In control rat myocytes, pretreatment with phorbol 12‐myristate 13‐acetate (PMA), an activator of protein kinase C (PKC), reduced the rate of Mn2+ quench to 68% of the untreated cell response. Pretreatment with GF109203X, a protein kinase C inhibitor, enhanced the rate of influx by 56%, whereas Gö6976, an inhibitor of PKC α, β, and γ, did not affect the rate of influx. By contrast, PMA did not affect the rate of Mn2+ quench in alcoholic myocytes; however, the PKC inhibitor GF109203X still enhanced the rate of Mn2+ quench by 33%. Similar to control myocytes, no effect was observed after pretreatment with Gö6976 in the alcoholic cells. In both Western blot and immunoprecipitation experiments, PKC ɛ expression in alcohol‐exposed myocytes was reduced to 68% of the control. However, the ratio of membrane/cytosolic distribution of PKC ɛ in alcoholic myocytes was increased from 1.6 to 2.6. No change was detected in the expression of PKC α and PKC δ. PKC activity, measured in the presence of Gö6976, which inhibits PKC α, β, and γ, was reduced in alcoholic myocytes to 57% of the control, but the proportion of PKC activity in the particulate fraction was increased from 26% in the control myocytes to 36% in the alcoholic myocytes.

Conclusions: Altered expression and activity of PKC may be associated with changes in the regulation of the cardiac Ca2+ channel found in the hearts of rats chronically exposed to alcohol. Specifically, we found that the novel class of PKC isozymes is responsible for regulating the cardiac Ca2+ channel in control cardiomyocytes, and that the loss of PMA modulation found in the alcoholic cells may be due, in part, to reduced expression and altered distribution of PKC ɛ.
The Development of an Ethanol Model Using Social Insects I: Behavior Studies of the Honey Bee (Apis mellifera L.)
Authors: Abramson Charles I. , Stone Sherril M. , Ortez Richard A. , Luccardi Alessandra , Vann Kyla L. , Hanig Kate D. , Rice Justin
Published: April 2006

Background: The purpose of this experiment was to test the feasibility of creating an animal model of ethanol consumption using social insects. Honey bees were selected as the model social insect because much is known about their natural history, physiology, genetics, and behavior. They are also inexpensive to procure and maintain. Of special interest is their use of communication and social organization.

Methods: Using both between‐ and within‐experiment designs, studies were conducted with harnessed foragers to determine whether honey bees would consume ethanol mixed with sucrose (and, in some cases, water). Shuttle‐box and running‐wheel studies were conducted to examine the effect of ethanol on locomotion. The effect of ethanol on stinging behavior in harnessed foragers was investigated. The effect of ethanol on Pavlovian conditioning of proboscis extension was also investigated. Finally, in a self‐administration study, foraging honey bees were trained to fly to an artificial flower containing ethanol.

Results: (1) Harnessed honey bees readily consume 1%, 5%, 10%, and 20% ethanol solutions; (2) 95% ethanol will also be consumed as long as the antennae do not make contact with the solution; (3) with the exception of 95% ethanol, consumption as measured by contact time or amount consumed does not differ in animals that consume 1%, 5%, 10%, and 20% ethanol solutions; (4) exposure to a lesser (or greater) concentration of ethanol does not influence consumption of a greater (or lesser) concentration; (5) consumption of 10% and 20% ethanol solutions decreases locomotion when tested in both a shuttle‐box and running‐wheel situation; (6) consumption of 1%, 5%, 10%, and 20% ethanol does not influence stinging behavior in harnessed foragers; (7) ethanol solutions greater than 5% significantly impair Pavlovian conditioning of proboscis extension; and (8) free‐flying honey bee foragers will readily drink from an artificial flower containing 5% ethanol.

Conclusions: The experiments on consumption, locomotion, and learning suggest that exposure to ethanol influences behavior of honey bees similar to that observed in experiments with analogous vertebrates. The honey bee model presents unique research opportunities regarding the influence of ethanol in the areas of language, social interaction, development, and learning. Although the behavioral results are interesting, similarity between the physiologic effects of ethanol on honey bees and vertebrates has not yet been determined.
Children's Hedonic Response to the Smell of Alcohol: Effects of Parental Drinking Habits
Authors: Mennella Julie A. , Garcia Pamela L.
Published: April 2006

Background: Previous research in our laboratory revealed that during the first year of life, infants who had more exposure to alcohol, as inferred from questionnaires about parental alcoholism and alcohol intake, mouthed an ethanol‐scented toy more compared with less exposed infants. The present study focused on older children (3.8–6.0 years) to determine whether their hedonic response to the odor of alcohol was related to the drinking habits of their parents.

Methods: Age‐appropriate, game‐like tasks that were fun for children and minimized the impact of language development were used to examine their preferences and identification of a variety of odors, one of which was beer.

Results: The children's preference for the odor of beer varied as a function of the escape drinking of their mothers alone or both parents. That is, children who lived in a household in which one or both parents drank alcohol to escape were significantly more likely to dislike the odor bottle that contained alcohol when compared with children whose parents did not drink to escape. This difference between the groups was odor specific. Additional analyses also revealed that the fathers of children who rejected the beer odor reported drinking significantly more than the fathers of those who liked the odor.

Conclusions: These findings suggest that some early learning about alcohol is based on sensory experiences and anchor it to children's experiences at home and the emotional context in which their parents experience alcohol.
Ethanol Reinforcement in Nondeprived Mice: Effects of Abstinence and Naltrexone
Authors: Middaugh Lawrence D. , Lee Allison M. , Bandy Angela‐Leigh E.
Published: April 2006

Background: Operant experiments which indicate that ethanol can serve as a reinforcer to maintain lever responding during limited periods of access have not been conducted on non‐food‐deprived mice, as they have for rats and monkeys. Furthermore, there are no reports of the effects of chronic ethanol and subsequent abstinence on ethanol reward in mice. Finally, although naltrexone reduces responding for ethanol in food‐deprived mice, the effects of the drug on ethanol reward for non‐food‐deprived mice have not been reported.

Methods: In three experiments, lever responding for ethanol (10–12%) was established in C57BL/6 (B6) mice by using either sucrose or saccharin fading procedures commonly used for rats. Experiment 1 examined both appetitive and consummatory responses while sucrose was faded from the ethanol solutions. Experiment 2 examined lever responding and ethanol intake (1) during saccharin fading; (2) when reinforcement schedules, reward availability, and primary conditioned reinforcers were manipulated; and (3) when mice were allowed chronic ethanol consumption followed by forced abstinence. Experiment 3 examined the effects of low doses of naltrexone on ethanol reward.

Results: Lever responding for ethanol can be established in non‐food‐deprived mice with the sucrose and saccharin fading procedures commonly used for rats. Lever responses increased with decreases in the reinforcer and increases in schedule demand, which indicated the reward value of the ethanol solution. Removal of ethanol from the solution reduced consumption with no change in the appetitive, instrumental response, which indicated that the two responses were under control of different stimuli, perhaps mediated by different neural mechanisms. Forced abstinence after chronic ethanol exposure increased responding for the drug, which suggested increased reward value. Naltrexone reduced responding as previously reported for food‐deprived B6 mice.

Conclusions: Ethanol appears to serve as a reinforcer for non‐food‐deprived or non‐water‐deprived B6 mice. Its reinforcing effects are increased by forced abstinence after chronic exposure and are decreased by naltrexone.
The Influence of Maternal Drinking and Drug Use on the Quality of the Home Environment of School‐Aged Children
Authors: Jester Jennifer M. , Jacobson Sandra W. , Sokol Robert J. , Tuttle Brenda S. , Jacobson Joseph L.
Published: April 2006

Background: Although many studies have examined the development of children of male alcoholics, few studies have considered substance use by the female caregiver. This study evaluated the relationship between substance use by female caregivers and factors that affect the child‐rearing environment.

Methods: A total of 480 inner‐city African‐American women were recruited during pregnancy for a longitudinal study of the effects of prenatal alcohol use and substance use by caregivers on the development of their children. All women were screened for alcohol consumption at their first prenatal visit to a large urban maternity hospital. Those who averaged seven or more drinks per week (0.5 oz absolute alcohol per day) at the time of conception were invited to participate in the study, as was a 5% random sample of lighter drinkers and abstainers. At the 7.5‐year follow‐up assessment, the quantity and frequency of alcohol consumption and drug use, as well as several measures of the child‐rearing environment, were assessed for 231 of the caregivers.

Results: Current alcohol use was uncorrelated with standard demographic factors, such as socioeconomic status, but was related to poorer family functioning, lower quality of parental intellectual stimulation, and higher levels of domestic violence. There were independent effects of illicit drug use on family environment, domestic violence, and caregiver depression. History of drinking during pregnancy, however, was not related to the current child‐rearing environment. Poorer parental functioning generally was found only among the caregivers who currently drank both heavily (six or more drinks/occasion) and frequently (three or more days/week). After controlling for lifetime alcohol problems, current drinking still predicted a less cohesive and organized family environment and higher levels of domestic violence.

Conclusions: Current heavy, frequent drinking in this relatively homogenous, economically disadvantaged sample was unrelated to demographics and seemed to have an important negative impact on the quality of the child‐rearing environment, whereas drinking during pregnancy was unrelated to the current child‐rearing environment.
In Vivo Detection and Functional Correlates of White Matter Microstructural Disruption in Chronic Alcoholism
Authors: Pfefferbaum Adolf , Sullivan Edith V. , Hedehus Maj , Adalsteinsson Elfar , Lim Kelvin O. , Moseley Michael
Published: April 2006

Background: Postmortem studies report degradation of brain white matter microstructure in chronic alcoholism, but until recently, in vivo neuroimaging could provide measurement only at a macrostructural level. The development of magnetic resonance diffusion tensor imaging (DTI) for clinical use offers a method for depicting and quantifying the diffusion properties of white matter expressed as intravoxel and intervoxel coherence of tracts and fibers.

Methods: This study used DTI to examine the intravoxel coherence measured as fractional anisotropy (FA) and intervoxel coherence (C) of white matter tracts of the genu and splenium of the corpus callosum and of the centrum semiovale in 15 detoxified alcoholic men and 31 nonalcoholic control subjects. Exploratory correlational analyses examined the relationships between regional DTI measures and tests of attention and working memory in the alcoholic patients.

Results: The alcoholic group had lower regional FA than the control group. C was lower in the alcoholics than controls in the splenium only. Working memory correlated positively with splenium FA, whereas attention correlated positively with genu C.

Conclusions: These results provide in vivo evidence for disruption of white matter microstructure in alcoholism and suggest that interruption of white matter fiber coherence contributes to disturbance in attention and working memory in chronic alcoholism.
Pregnant, Alcohol‐Abusing Women
Authors: Hankin Janet , McCaul Mary E. , Heussner Janet
Published: April 2006

Background: This paper reviews the literature on the identification and treatment of pregnant, alcohol‐abusing women, with special emphasis on poor women who have access to treatment through Medicaid.

Methods: The paper discusses the gaps and controversies in the literature and suggests five priorities for future research.

Results: Studies that attempt to identify pregnant women who drink conclude that heavier drinkers enter prenatal care later than other women, that many health care providers fail to recognize alcohol abuse by pregnant women, and that research on screening techniques is still in the early stages. Treatment research suggests that comprehensive, holistic treatment approaches, as well as brief interventions and case management, have been successful in reducing prenatal alcohol use. Debate continues over whether treatment should be voluntary.

Conclusions: The five areas identified as priorities for future research include (1) developing reliable and valid measures to identify alcohol abuse in pregnant women, (2) creating training programs for providers, (3) generating programs to reduce barriers to care, (4) determining which treatment programs are most successful, and (5) estimating the costs and benefits of various treatment approaches.
Welfare Reform and the Changing Landscape of Substance Abuse Services for Low‐Income Women
Authors: Schmidt Laura A. , McCarty Dennis
Published: April 2006

Recent welfare reform policies could fundamentally change the nature of public‐sector substance abuse services available to women. This review summarizes what is presently known about substance abuse services and women on welfare, and identifies limitations in our current knowledge about the potential effects of welfare reform. Five crucial areas are examined in which research on services has fallen short: (1) assessing the need for substance abuse services across a broad spectrum of welfare populations, (2) exploring the role that alcohol and drug problems play in welfare dependency, (3) examining how welfare programs can serve as pathways to alcohol and drug treatment, (4) evaluating the effectiveness and costs of innovative welfare‐treatment programs, and (5) understanding systems‐level adaptations in substance abuse services for women that result from changing welfare policies. We conclude that researchers who study services should take a broad view of these issues—one that considers the unique situation of poor women and single mothers, that views substance abuse within a work impairment or disabilities framework, and one that is attuned to future changes in the effects of welfare reform as the economy and labor markets undergo change.
Mapping of Quantitative Trait Loci for Hypnotic Sensitivity to Ethanol in Crosses Derived From the C57BL/6 and DBA/2 Mouse Strains
Authors: Radcliffe Richard A. , Bohl Michelle L. , Lowe Mark V. , Cycowski Colleen S. , Wehner Jeanne M.
Published: April 2006

Background: Acute ethanol sensitivity is thought to be a predisposing factor toward the development of alcoholism. Accumulated evidence suggests that this characteristic may be at least partly heritable. A widely accepted approach for identifying genes thought to contribute to alcoholism is to map quantitative trait loci (QTLs) for various ethanol‐related behaviors in rodent models.

Methods: Ethanol sensitivity QTLs were interval‐mapped in a C57BL/6 (B6) × DBA/2 (D2) F2 intercross that contained 391 mice. Sensitivity was measured as the duration of loss of righting reflex (LORR) after 4.1 g/kg ip. LORR also was evaluated in a chromosome 1 marker‐assisted congenic strain that had an approximately 30 centiMorgan (cM) portion of D2 DNA from the distal end of chromosome 1 introgressed onto a B6 background.

Results: A suggestive QTL was mapped on chromosome 1 (LOD = 3.3; ∼80 cM) and a provisional QTL on chromosome 5 (LOD = 2.3; ∼26 cM). The provisional chromosome 5 QTL was found to be sex‐specific (LOD = 2.5 for males; LOD < 1 for females) with the D2 allele increasing LORR. The chromosome 1 D2 allele decreased LORR. Consistent with the F2 QTL mapping, congenic mice heterozygous for the chromosome 1 interval (B6/D2) had a significantly different mean (±SEM) LORR of 74.0 ± 4.9 min (n= 36) compared with 90.8 ± 6.2 min (n= 33) for their homozygous (B6/B6) littermates (p= 0.02). Blood ethanol concentration at regain of righting reflex was 377 ± 10 mg% for the B6/D2 and 368 ± 10 mg% (p= NS) for the B6/B6.

Conclusions: LORR results in the chromosome 1 congenic mice were consistent with and very similar to what was predicted from the QTL analysis in the B6 X D2 F2 population. These results support a suggestive LORR QTL on the distal end of mouse chromosome 1. The results also indicate that there is a provisional sex‐specific LORR QTL on chromosome 5.
Polysomnographic and Spectral Sleep EEG in Primary Alcoholics: An Interaction Between Alcohol Dependence and African‐American Ethnicity
Authors: Irwin Michael , Miller Claudine , Gillin J. Christian , Demodena Anna , Ehlers C. L.
Published: April 2006

Background: Disturbances of sleep EEG are prominent in alcoholic patients, persist into recovery, and recently have been found to predict those alcoholics who are most likely to relapse. Increasing evidence indicates that there are ethnic differences in sleep EEG and that African‐Americans may be at elevated risk for disordered sleep.

Methods: This study compared polysomnographic and spectral sleep EEG measures in male primary alcoholic inpatients (n= 31) and age‐matched comparison controls (n= 31) stratified by African‐American and Euro‐American ethnicity.

Results: African‐American alcoholic patients showed more severe sleep abnormalities than Euro‐American alcoholics, and the interaction between alcohol dependence and ethnicity uniquely contributed to prolonged sleep latency (p < 0.001), loss of delta sleep (p < 0.001), and short rapid eye movement (REM) latency (p < 0.001). Spectral EEG analyses confirmed polysomnographic findings of disordered sleep architecture in alcoholics. Compared with controls, alcoholics had lower delta (0.75–4.5 Hz) activity over the whole night (p < 0.05), reductions in mean spectral power (0.75–40 Hz, p < 0.05), and decreases of delta (p < 0.01) and theta (4.5–7.5 Hz, p= 0.05) activity during the first period of non‐REM sleep, with African‐American alcoholics having the lowest theta of the four groups.

Conclusions: In view of the possible connection between relapse and poor sleep and the role of sleep in the maintenance of health, these data have implications for treatment and morbidity outcomes in African‐American alcoholics.
Sex Differences of Carbohydrate‐Deficient Transferrin, γ‐Glutamyltransferase, and Mean Corpuscular Volume in Alcohol‐Dependent Patients
Authors: Mundle Götz , Munkes Jörg , Ackermann Klaus , Mann Karl
Published: April 2006

Background: Biological markers like carbohydrate‐deficient transferrin (CDT), γ‐glutamyltransferase (GGT), and mean corpuscular volume (MCV) are used widely to screen for alcoholism. Most research has focused on male alcoholics, and there are few studies on female patients. The results are inconsistent; in general, they show lower sensitivities for all markers for women.

Methods: We compared the diagnostic value of CDT, GGT, and MCV in 126 alcohol‐dependent patients (91 men, 35 women) who entered an inpatient treatment program. For the receiver operating characteristic (ROC) analyses, we investigated a control group of 112 patients (64 men, 38 women) from the Department of Psychiatry at the University of Tübingen with no diagnosis of substance abuse or substance dependency.

Results: Mean levels of CDT and MCV were significantly different in male and female patients. CDT showed higher test results in men (4.4% vs. 2.8%, p < 0.05), whereas mean levels of MCV were higher in women (99.7 fl vs. 96.4 fl, p < 0.01). The sensitivities of CDT and GGT were higher in men than in women (CDT: 76% vs. 54%, p < 0.1; GGT: 68% vs. 43%, p < 0.05), and the sensitivity of MCV was significantly higher in women (71% vs. 41%, p < 0.01). The superiority of MCV in women also was supported by ROC analyses (p < 0.01). The combined use of markers showed satisfactory sensitivity rates of ≥80% not only in men but also in women. Yet, the specificity rates were partly below the recommended 90% for identifying alcohol abuse; therefore, these markers must be combined with caution.

Conclusions: If combined, the biological markers CDT and GGT are useful diagnostic instruments for both alcohol‐dependent men and women. According to our results, the “forgotten” marker MCV is superior in women and is a marker of second choice in men. The combination GGT and MCV is the most cost‐effective choice for men and women.
Validity of Self‐Reported Alcohol Consumption in Nondependent Drinkers With Unintentional Injuries
Authors: Sommers Marilyn Sawyer , Dyehouse Janice M. , Howe Steven R. , Lemmink Jennifer , Volz Tina , Manharth Marjorie
Published: April 2006

Background: Self‐report has become an anchor for alcohol assessment in the acute and primary care populations. The purpose of the study was to determine the validity of self‐reported alcohol consumption after unintentional injuries in hospitalized, nondependent drinkers.

Methods: Non‐alcohol‐dependent subjects 18 years of age and older with unintentional injuries (n= 209) were enrolled in the study and were interviewed if they had either an admitting blood alcohol concentration (BAC) ≥ 10 mg/dl (0.01 g/dl) or a positive screen for a history of problem drinking. The self‐reported number of standard drinks, time that drinking commenced, sex, and weight were used to calculate estimated blood alcohol concentration (EBAC), which was then compared to the admission BAC.

Results: We had data to calculate the EBAC on 141 of the 209 subjects. Seven men and no women with positive (≥10 mg/dl) BAC denied drinking. Of the 134 subjects for whom we had data to calculate EBAC and who acknowledged drinking, mean BAC was 147.06 mg/dl and mean EBAC was 68.66 mg/dl. For women (n= 30), mean BAC was 149.53 mg/dl and mean EBAC was 114.67 mg/dl; for men (n= 104), mean BAC was 146.35 mg/dl and mean EBAC was 55.38 mg/dl. The Spearman's ρ between laboratory BAC and EBAC was 0.461 (p < 0.001) for all subjects (n= 134), 0.275 (NS) for women (n= 30), and 0.532 (p < 0.001) for men (n= 104). For women and men separately, multiple regression analyses were performed to predict BAC by using weight and reported number of drinks. For women, weight and number of drinks accounted for 3% of the variance in laboratory BAC [r= 0.181, F (2,47) = 0.797, p= NS]. In contrast, for men these same predictors accounted for 34% of the variance [r= 0.585, F (2,135) = 35.203, p < 0.001).

Conclusions: Most nondependent patients with unintentional injury acknowledged drinking before injury. After injury, women and men have different patterns of reporting their drinking, with men more frequently underreporting but reporting more accurately and women more random in their self‐reports.
Dose‐Dependent Effect of Ethanol on Hepatic Oxidative Stress and Interleukin‐6 Production After Burn Injury in the Mouse
Authors: Colantoni Alessandra , Duffner Lisa A. , de Maria Nicola , Fontanilla Christine V. , Messingham Kelly A. N. , Van Thiel David H. , Kovacs Elizabeth J.
Published: April 2006

Background: Burned patients with detectable blood alcohol levels (BAL) show an elevated mortality rate. Interleukin (IL)‐6 and reactive oxygen species (ROS) production is stimulated independently by alcohol and burn injury. The aim of the study was to determine whether increasing levels of alcohol differentially enhance the hepatic production of IL‐6 and ROS after burn in a murine model of dorsal scald injury. Groups of mice received either saline or alcohol intraperitoneally to reach a BAL of 100 mg/dl or 300 mg/dl at the time of burn (15% total body surface scald) or sham injury.

Results: Burn injury alone resulted in a low mortality rate at 24 hr after injury as did the burn group with a BAL of 100 mg/dl (15%), whereas 57% of the mice burned with a BAL of 300 mg/dl did not survive (p= 0.02). Twenty‐four hours after burn or sham injury, IL‐6 levels were measured by enzyme‐linked immunosorbent assay in serum and liver. In the saline‐treated group, IL‐6 circulating and hepatic levels rose after burn injury (p < 0.03). Circulating IL‐6 levels in sham mice increased 1.5‐fold in the group with a BAL of 100 mg/dl and 3‐fold in those with a BAL of 300 mg/ml (p= 0.005 versus burn‐injured, saline‐treated). IL‐6 hepatic production after burn injury was higher in the mice with a BAL of 300 mg/dl than in those with a BAL of 100 mg/dl and the saline‐treated group (p= 0.001). Among the burned mice, alcohol exposure increased hepatic ROS production, measured by lipid peroxidation and protein oxidation, in a dose‐dependent manner.

Conclusions: Alcohol enhances in a dose‐dependent manner the hepatic production of IL‐6 induced by burn injury through the modulation of oxidative stress. The increased mortality rate of mice exposed to alcohol and burn injury may be due to the adverse effect on immune function induced by IL‐6 elevation.
Influence of Sex Hormonal Status on Alcohol‐Induced Oxidative Injury in Male and Female Rat Liver
Authors: Colantoni Alessandra , La Paglia Nancy , de Maria Nicola , Emanuele Mary Ann , Emanuele Nicholas V. , Idilman Ramazan , Harig James , Van Thiel David H.
Published: April 2006

Background: Oxidative stress contributes to the development of liver injury after chronic alcohol intake. Women exhibit greater sensitivity to alcohol‐induced liver disease than do men. The aim of the study was to determine the relationship between the sex hormone status of male and female rats and the degree of alcohol‐induced oxidative stress in the liver.

Methods: Male and female rats were pair‐fed a liquid diet that contained 36% of their total daily calories as ethanol (EtOH group) or maltose (control group). Blood and liver samples were collected at the end of 8 weeks of diet.

Results: Male EtOH rats experienced a reduction in plasma testosterone (T) and an increase in estradiol (E2) levels, with an increase in their calculated E2/T ratio with respect to their controls. Malonaldehyde (MDA) levels, an index of lipid peroxidation, and protein carbonyl content, an index of protein oxidation, in the liver were greater among the EtOH groups in females than in males. In males, an inverse correlation was found between hepatic MDA and circulating T levels, and a direct correlation was disclosed between MDA and estradiol levels. In addition, the hepatic histopathological score correlated inversely with the plasma T levels and directly with the calculated E2/T ratio, an index of feminization.

Conclusions: Alcohol‐induced oxidative injury, which contributes to hepatic injury in both male and female rats, is enhanced in females compared with males. A role for plasma T levels in protecting male rat liver from ethanol‐induced oxidative injury can be hypothesized.
A Comparison of Correlates of DSM‐IV Alcohol Abuse or Dependence Among More Than 400 Sons of Alcoholics and Controls
Authors: Schuckit M. A. , Smith Tom L.
Published: April 2006

Background: Alcohol dependence and abuse are defined as separate disorders. However, relatively few data are available about whether the same characteristics predict both syndromes.

Methods: Complete data were available from the 15 year follow‐up of 411 men who originally had been evaluated from a university population at about age 20. Both baseline data gathered prospectively and the retrospective ratings in six domains of life functioning were analyzed for their relationship to the development of alcohol abuse or dependence during the follow‐up.

Results: Baseline characteristics of a family history of substance use disorders, the quantity and frequency of drinking, the history of alcohol‐related problems, and the level of response to alcohol all predicted future alcohol abuse or dependence, but only an alcoholic second‐degree relative or a first‐degree drug‐dependent family member differentially predicted dependence. Logistic regression analyses revealed that similar baseline characteristics combined to predict dependence and, separately, abuse. When the domains of functioning during the 15 years were included, positive alcohol expectancies, poor coping mechanisms, low level of social support, and drinking in the environment contributed to both dependence and abuse, although the relationship was stronger for dependence.

Conclusions: The predictors and correlates of alcohol abuse and dependence in this group of men were similar. Further research in additional populations and on other drugs is needed to determine if the two syndromes overlap sufficiently to be combined.
Pretreatment With Hydromorphone, a μ‐Opioid Agonist, Does Not Alter the Acute Behavioral and Physiological Effects of Ethanol in Humans
Authors: Rush Craig R.
Published: April 2006

Background: Endogenous opioid systems are thought to mediate at least some of the behavioral effects of ethanol. Opioid antagonists, like naloxone and naltrexone, decrease ethanol self‐administration under a variety of conditions in different species of laboratory animals (e.g., rodents and nonhuman primates). Opioid agonists, like morphine, also alter ethanol consumption. However, the dose‐response functions for opioid agonists are complex in that low doses increase ethanol self‐administration, whereas moderate to high doses decrease ethanol self‐administration. The results of prospective human laboratory studies that assessed the behavioral effects of ethanol after pretreatment with an opioid antagonist are mixed. The aim of the present study was to assess the acute subject‐rated effects of ethanol (0, 0.5, and 1 g/kg) after pretreatment with hydromorphone, a μ‐opioid agonist.

Methods: In the present experiment, the acute subject‐rated, performance‐impairing, and physiological effects of ethanol (0, 0.5, and 1 g/kg) were examined after pretreatment with hydromorphone (0, 1, and 2 mg), a μ‐opioid agonist, in nine healthy volunteers. Volunteers received one of the nine possible ethanol‐hydromorphone combinations during each of nine experimental sessions.

Results: Ethanol produced prototypical subject‐rated drug effects (e.g., dose dependently increased ratings of “high”), impaired performance, and increased heart rate. Hydromorphone pretreatment generally did not significantly alter the subject‐rated, performance‐impairing, or physiological effects of ethanol.

Conclusions: The results of the present experiment suggest that hydromorphone pretreatment does not significantly affect the subject‐rated effects of ethanol. Future human laboratory studies should test higher doses of hydromorphone. Future studies also might use more sophisticated behavioral procedures like self‐administration, or perhaps drug discrimination, to determine if opioid agonists can modulate the behavioral effects of ethanol in humans.
Adverse Drinking Consequences Among Alcohol Abusing Intravenous Drug Users
Authors: Anderson Bradley J. , Gogineni Aruna , Charuvastra Anthony , Longabaugh Richard , Stein Michael D.
Published: April 2006

Background: Heavy alcohol use is common among out‐of‐treatment injection drug users (IDUs); however, the relationship between alcohol and drug use behaviors in codependent populations is not well understood. Our specific objectives were (1) to describe the psychometric properties of the Drinker Inventory of Consequences (DrInC) in a sample of active IDUs, and (2) to compare DrInC scores of active IDUs with those reported for the alcohol treatment seeking sample on which the instrument was developed.

Methods: Interview data were collected from 187 active IDUs who scored positively (≥ 8) on the Alcohol Use Disorders Identification Test, who were recruited from a Providence, RI, needle exchange program (1998–1999). DrInC total and subscale scores for the 159 (85%) participants who met DSM‐IV criteria for alcohol abuse/dependence were analyzed. Six‐month follow‐up data were used to estimate test‐retest reliability.

Results: The DrInC total scale exhibited high internal consistency and test‐retest reliability. With the exception of adverse physical consequences, reliability estimates for DrInC subscales were good to very good. These data indicate higher subscale redundancy than reported for the development sample. Active IDUs had significantly higher adverse impulse control consequences than the alcohol treatment seeking population on which the instrument was developed.

Conclusions: The DrInC exhibits desirable psychometric properties for assessing adverse drinking consequences in active IDU populations. IDUs who met DSM‐IV criteria for alcohol abuse/dependence reported overall levels of adverse drinking consequences comparable with non‐IDU alcohol treatment populations but were more likely to exhibit adverse impulse control consequences.
Effects of Chronic Alcohol Consumption on the Broad Phospholipid Signal in Human Brain: An In Vivo 31P MRS Study
Authors: Estilaei M. R. , Matson G. B. , Payne G. S. , Leach M. O. , Fein G. , Meyerhoff D. J.
Published: April 2006

Background: Phosphorus magnetic resonance spectroscopy (31P MRS) allows for the measurement of phospholipids and their breakdown products in the human brain. Fairly mobile membrane phospholipids give rise to a broad signal that co‐resonates with metabolic phosphodiesters. Chronic alcohol exposure increases the rigidity of isolated brain membranes and, thus, may affect the amount and transverse relaxation times (T2) of MRS‐detectable phospholipids. We tested the hypothesis that subjects who were heavy drinkers have stiffer membranes than controls who were light drinkers, as reflected in a smaller broad signal component and a shorter T2 of the broad signal in 31P MR spectra of the brain.

Methods: Thirteen alcohol‐dependent heavy drinkers (mean age 44 years) were studied by localized 31P MRS in the centrum semiovale and compared with 17 nondependent light drinkers of similar age. The broad component signal was separated from the metabolite signal by convolution difference, which is based on the large difference in line widths of these two signals. Longitudinal and T2 relaxation times were measured using standard methods.

Results: The broad component integral was 13% lower in the brain of heavy drinkers compared with light drinkers (p < 0.001) and remained significantly smaller after corrections for both longitudinal and transverse relaxations (p < 0.01). The T2 distribution of the broad component consistently showed two resolvable components in both groups. The fast relaxing component had the same T2 in both groups (T2= 1.9 msec). The slower relaxing component T2 was 0.6 msec shorter in heavy drinkers compared with light drinkers (p= 0.08).

Conclusions: These results, observed in the absence of white matter volume loss, are consistent with biochemical alterations and higher rigidity of white matter phospholipids associated with long‐term chronic alcohol abuse. The observed smaller broad signal component in these relatively young heavy drinkers is a sensitive measure of white matter phospholipid damage.
Thiamin Treatment and Working Memory Function of Alcohol‐Dependent People: Preliminary Findings
Authors: Ambrose Margaret L. , Bowden Stephen C. , Whelan Greg
Published: April 2006

Background: Wernicke‐Korsakoff syndrome (WKS) is most often seen in people who are alcohol dependent. Treatment with thiamin may rapidly resolve acute symptoms. However, much evidence suggests that identification of WKS on clinical examination is relatively insensitive when compared with diagnosis at postmortem. No study has investigated the therapeutic effect of thiamin in a sample of alcohol‐dependent people without the clinical triad of acute WKS.

Methods: We conducted a randomized, double‐blind, multidose study of thiamin treatment in 107 subjects who were detoxifying from alcohol. Five groups of subjects were assessed with the Mini‐Mental State Examination and were examined for the presence of neurological signs. Subjects were given different doses of intramuscular thiamin for two consecutive days. The posttreatment performance of these groups then was examined on a test of working memory derived from comparative neuropsychology, namely, the delayed alternation task. This test has been established as sensitive to the neuropathology of WKS.

Results: Pretreatment measures of mental status and neurological signs were equivalent across groups. Groups were equated with respect to the background variables of age, education, typical daily alcohol consumption, and years of drinking. On the posttreatment measure, a superior performance was found in the group that received the highest dose of thiamin, compared with the other four treatment groups.

Conclusions: A therapeutic relationship between dose and working memory performance was indicated. These results have important implications for the management and prevention of WKS, but further investigations are needed to substantiate the nature of the therapeutic relationship.