bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.