bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of Dopamine D2 Autoreceptors in the Ventral Tegmental Area on Alcohol and Saccharin Intake of the Alcohol‐Preferring P Rat
Authors: Nowak K. L. , McBride W. J. , Lumeng L. , Li T.‐K. , Murphy J. M. 
Published: April 2006

Background: The ventral tegmental area (VTA) dopamine (DA) system is considered to be involved in mediating the actions of ethanol (EtOH). The objective of the present study was to examine the role of VTA DA D2 receptors in regulating EtOH intake of alcohol‐preferring P rats.Methods: EtOH (10% v/v) and saccharin (SACC, 0.0125% g/v) intake during 2 hr of limited access was assessed after microinjections of the D2 agonist quinpirole and the D2 antagonist sulpiride into the anterior VTA (AVTA) of female P rats. Both EtOH‐SACC alternate‐day‐access conditions and daily availability of EtOH and SACC solutions to separate groups of subjects were used. A second D2 agonist, quinelorane, and coadministration of 2.0 μg sulpiride with 2.0 μg quinpirole were tested in animals given limited access to EtOH. Finally, the effects of quinpirole injected 2 mm dorsal to the VTA and within the posterior VTA (PVTA) were assessed under EtOH‐SACC alternate‐day‐access conditions.Results: Microinjections of 2.0–6.0 μg quinpirole into the AVTA dose dependently decreased EtOH intake 40–80% during the first 30 min of the limited access sessions but did not alter SACC intake. Injections of 2.0–4.0 μg quinelorane into the AVTA also reduced EtOH intake in the first 30 min. Administration of 0.5–2.0 μg sulpiride into the AVTA had no effect on either EtOH or SACC intakes but did attenuate the effects of quinpirole on reducing EtOH intake. Injections of 2.0–4.0 quinpirole 2 mm dorsal to the VTA did not alter EtOH or SACC intakes. Posterior VTA injections of quinpirole decreased EtOH and SACC intakes approximately 25–30% and 60–70%, respectively, in the first 30 min. None of the treatments altered intakes during the 30–120 min period.Conclusions: The data suggest that DA neuronal activity within the AVTA may be important for maintaining EtOH drinking in P rats, whereas DA neuronal activity within the PVTA may be involved in regulating general drinking and/or motivational behaviors. Overall, the results confirm the involvement of mesolimbic DA in EtOH self‐administration and suggest that there is functional heterogeneity within the VTA regulating drinking behavior of the P rat.
Carbohydrate‐Deficient Transferrin, γ‐Glutamyltransferase, and Macrocytic Volume as Biomarkers of Alcohol Problems in Women
Authors: Allen John P. , Litten Raye Z. , Fertig Joanne B. , Sillanaukee Pekka 
Published: April 2006

Background: Early identification of alcohol problems in women is important. Differences in patterns of drinking and in biological function between genders, however, may present unique difficulties in biochemical screening.Methods: Published alcohol‐screening studies with female samples and use as biomarkers of carbohydrate‐deficient transferrin (CDT), γ‐glutamyltransferase (GGT), and macrocytic volume were reviewed.Results: A wide range of sensitivities and specificities of GGT and CDT have been reported, although, in general, the two markers seem approximately equal in accuracy. As in the case of males, use of them in combination substantially enhances sensitivity and little reduces specificity. Use of macrocytic volume improves the sensitivity of both GGT and CDT as alcohol‐screening markers.Conclusions: GGT and CDT have moderate sensitivity in screening for alcohol problems in women. Use of them in concert offers further advantage.
Personality, Family History, and Alcohol Use Among Older Men: The VA Normative Aging Study
Authors: LoCastro Joseph , Spiro Avron , Monnelly Edward , Ciraulo Domenic 
Published: April 2006

Background: We examined personality traits (Sociability, Impulsivity, Neuroticism) as mediators of the effects of family history on alcohol outcomes.Methods: A sample of 485 men reported on family history of alcohol problems in 1973, completed the Eysenck Personality Inventory in 1976, and responded to a survey on alcohol use in 1982.Results: Using structural equation modeling, family history was found to have direct effects on number of drinks per day and on the number of alcohol problems, as well as indirect effects mediated through Neuroticism. There were no effects of Sociability or Impulsivity on either alcohol outcome.Conclusions: In this sample of older men, family history had both direct and indirect effects, and personality traits found to affect alcohol outcomes were different from those that have been found in younger men.
Expansions of CD8CD28− and CD8TcRVβ5.2 T Cells in Peripheral Blood of Heavy Alcohol Drinkers
Authors: Arosa Fernando A. , Porto Graça , Cabeda José Manuel , Lacerda Rosa , Resende Dolores , Cruz Eugenia , Cardoso Carla , Fonseca Mafalda , Simões Carla , Rodrigues Pedro , Bravo Fernanda , Oliveira José Carlos , Alves Helena , Fraga José , Justiça Benvindo , de Sousa Maria 
Published: April 2006

Background: Despite heavy alcohol consumption, only a low percentage of heavy drinkers develop liver disease. Imbalances in T‐cell subsets and iron metabolism parameters are common findings in heavy drinkers, yet the possible role played by discrete T‐lymphocyte subsets under heavy alcohol consumption remains unclear.Methods: To gain new insights into the possible role played by T lymphocytes during alcohol consumption, characterization of CD28 expression and TcR repertoire in peripheral blood CD4+ and CD8+ T cells by two and three‐color flow cytometry was performed. A group of heavy alcohol drinkers (AHD, n= 71) and a group of age‐matched controls (n= 81), both HLA‐phenotyped and HFE‐genotyped, constituted the groups under study.Results: Marked expansions of CD28− T cells within the CD8+ but not the CD4+ T‐cell pool were observed in AHD compared with controls. These CD8+CD28− expansions were paralleled by expansions of CD8+ T cells bearing specific TcR Vα/β chains, namely Vβ5.2. Moreover, AHD, but not controls, carrying the H63D mutation in the HFE gene showed significantly higher percentages of CD28− T cells within the CD8+ T‐cell pool than AHD carrying the normal HFE gene. Finally, high numbers of CD8+CD28− T cells in AHD were associated with lower levels of the liver‐related enzymes ALT and GGT.Conclusions: This study showed that under active ethanol consumption, expansions of discrete CD8+ T‐cell subsets occur within the CD8+ T‐cell pool, that molecules of the MHC‐class I locus seem to influence the extent of the expansions, and that high numbers of CD8+CD28− T cells are associated with low levels of liver enzymes in AHD.
Ethanol Induces Fas/Apo [Apoptosis]‐1 mRNA and Cell Suicide in the Developing Cerebral Cortex
Authors: Cheema Zulfiqar F. , West James R. , Miranda Rajesh C. 
Published: April 2006

Introduction Animal studies modeling fetal alcohol syndrome have demonstrated that developmental exposure to alcohol is associated with decreased brain weight and significant neuronal loss in multiple regions of the developing brain. Our previous data suggest that the Fas/Apo [apoptosis]‐1 receptor is transiently expressed in the developing cerebral cortex during the peak period of naturally occurring apoptotic cell death and maximum sensitivity to alcohol. Therefore, we hypothesized that ethanol increases the expression of suicide receptors such as Fas/Apo‐1 in the developing fetal cerebral cortex and leads to an upregulation or extension of the normal period of apoptosis and consequent disorganization of the neural circuitry.Methods: Ethanol was administered in one of four doses (120, 320, 630, and 950 mg/dl) to organotypic explant cultures of the developing cerebral cortex established from postnatal day 2 rats and maintained for 6 days in vitro. The number of cells expressing Fas/Apo‐1 receptor mRNA was counted. Apoptosis was measured by the use of two independent assays; a cell death enzyme‐linked immunosorbent assay for DNA fragmentation and flow cytometric analysis of Annexin‐V binding to phosphatidylserine externalized to the outer leaflet of the plasma membrane. Necrosis was also estimated by two independent measures, the amount of lactate dehydrogenase released into culture medium and flow cytometric analysis of cells that were positive for both Annexin‐V and propidium iodide.Results: A significantly larger number of developing cortical cells expressed Fas/Apo‐1 mRNA at the lower doses (120 and 320 mg/dl) than at the higher doses (630 and 950 mg/dl). Furthermore, ethanol induced apoptosis in a dose‐related manner, with peak apoptosis observed at a dose of 630 mg/dl in the case of DNA fragmentation and at 630 and 950 mg/dl in the case of phosphatidylserine translocation to the outer leaflet of the plasma membrane. Ethanol did not induce necrosis at any of the administered doses of ethanol.Conclusions: Our data suggest that ethanol induces a susceptibility to apoptotic signals at low doses by upregulating the expression of mRNAs for cytotoxic receptors such as Fas/Apo‐1 in the developing cerebral cortex. However, ethanol itself specifically induces apoptosis in the developing cerebral cortex only at higher doses.
Ethanol and Murine Interleukin (IL)‐12 Production
Authors: Mason Carol M. , Dobard Elizabeth , Kolls Jay K. , Nelson Steve 
Published: April 2006

Background: Interleukin (IL)‐12 is a cytokine with protean effects against bacterial and intracellular pathogens. Induction of IL‐12 at the time of infection has salient effects on elimination of various microbes. This work describes the effect of exposure to ethanol on lipopolysaccharide (LPS)‐induced production of IL‐12 in mice and whether ethanol‐induced increases in IL‐10 mediates these changes in IL‐12 production.Methods: BALB/c mice were pretreated with ethanol and then challenged with LPS either intravenously (iv) or intratracheally (it), and blood and lung production of IL‐12 (p70 and p40 components) and serum IL‐10 were assayed. Splenic and lung mRNA for IL‐12 p35 and p40 components was determined.Results: Ethanol pretreatment suppressed LPS‐induced IL‐12 p70 and p40 protein production in blood and lung. In spleen and lung, p40 mRNA was induced to a greater extent than p35 mRNA, and there was greater suppression of p40 mRNA compared with p35 mRNA in ethanol‐treated animals. Ethanol up‐regulated the production of IL‐10, and pretreatment of these animals with a polyclonal anti‐IL‐10 antibody resulted in significant increases in IL‐12 p70 and p40 levels, but not completely to those of control animals.Conclusions: Ethanol suppresses the production of murine IL‐12 in response to LPS in blood and lung, with both the p70 and the p40 components affected. This suppression is accompanied by reductions of p40 mRNA in both spleen and lung. IL‐10 may play a role in ethanol‐induced suppression of IL‐12, as neutralization of IL‐10 partially attenuated the suppression of IL‐12.
Decreased Natural Killer Cell Responses and Altered Interleukin‐6 and Interleukin‐10 Production in Alcoholism: An Interaction Between Alcohol Dependence and African‐American Ethnicity
Authors: Irwin Michael , Miller Claudine 
Published: April 2006

Background: Epidemiological data indicate that among alcoholics African‐American men have higher rates of infections compared with white alcoholics. Alcohol is thought to reduce natural killer (NK) cell responses and to alter cellular immunity by changing the relative balance of Th1 versus Th2 cytokine response profiles. However, translation of these basic immunological observations into the clinical setting is limited, and what clinical data are available are contradictory, in part, because of heterogeneity within the alcoholic patient population. Whether ethnic characteristics contribute to variation in the immunological effects of alcohol is not known.Methods: This study compared NK activity, interleukin (IL)‐2–stimulated NK activity, and concanavalin A–stimulated peripheral blood mononuclear cell production of Th1 (IL‐12 and IL‐2), Th2 (IL‐10), and proinflammatory (IL‐6) cytokines in 31 hospitalized chronic alcoholic patients and 31 age‐matched controls who were stratified on the basis of ethnicity.Results: NK‐cell responses were significantly different across the four groups, and African‐American alcoholics showed the lowest levels of NK activity (F= 9.5;p < 0.001) and IL‐2–stimulated NK activity (F= 2.9;p < 0.05). Compared with the other three groups, African‐American alcoholics also showed lower levels of IL‐6 (F= 7.2;p < 0.01) and higher levels of IL‐10 (F= 4.9;p < 0.05). Stimulated production of IL‐2 and IL‐12 were similar in the four groups. Regression analyses showed that alcohol dependence and ethnicity predicted NK activity, whereas the interaction between alcohol dependence and ethnicity predicted levels of IL‐6 and IL‐10.Conclusions: In summary, the immunological effects of alcohol dependence are modified by ethnicity status, consistent with the increased health risks found in African‐American alcoholics.
The Genetics of Acute Functional Tolerance and Initial Sensitivity to Ethanol for an Ataxia Test in the LSxSS RI Strains
Authors: Gehle Vaughn M. , Erwin V. Gene 
Published: April 2006

Background: It has been proposed that development of tolerance to the behavioral effects of ethanol depends on the degree of impairment produced by the drug; that is, more sensitive individuals should develop greater tolerance. Tests of this hypothesis with respect to acute functional tolerance have produced contradictory results. We tested the hypothesis by examining the genetic relationship between initial sensitivity and acute functional tolerance in the LSXSS recombinant inbred mice.Methods: We tested mice for initial sensitivity to the ataxic effects of 1.75 g/kg of ethanol in a stationary dowel balance test by determining blood and brain ethanol concentrations at fall. Acute tolerance to the ataxic effects of ethanol was determined by measuring blood ethanol concentration (BEC) at regain of dowel balance ability after the first injection (BEC1RB) and after a second ethanol injection of 2.0 g/kg (BEC2RB). Acute tolerance was quantified by the difference in ethanol concentration at the two regains of balance (BEC2RB − BEC1RB) or by the difference between the second regain and one of the initial sensitivity measures (BEC2RB − initial sensitivity).Results: Four different measures of initial sensitivity were taken: two that used BEC values and two that used forebrain or hindbrain ethanol concentrations. We calculated acute tolerance values by using each of these initial sensitivity measures plus BEC2RB. No evidence of a genetic relationship between initial sensitivity and acute tolerance was found, which suggests that these are two independent phenomena with respect to stationary dowel balance.Conclusions: Three conclusions can be drawn from this work: (1) Orbital sinus BEC at early time points (<5 min postinjection) may or may not accurately reflect brain EC in mice, dependent on genotype; (2) there is no genetic relationship between initial sensitivity and acute tolerance to stationary dowel ataxia in the LSXSS RIs; and (3) sex‐specific factors affect low‐dose ethanol responses on the stationary dowel.
Norepinephrine Uptake Sites in the Locus Coeruleus of Rat Lines Selectively Bred for High and Low Alcohol Preference: A Quantitative Autoradiographic Binding Study Using [3H]‐Tomoxetine
Authors: Hwang Bang H. , Wang Guo‐Ming , Wong David T. , Lumeng Lawrence , Li T.‐K. 
Published: April 2006

Background: The locus coeruleus (LC) is the largest norepinephrinergic cell group in the central nervous system and contains a high density of norepinephrine (NE) uptake sites. Alcohol‐preferring (AP) rats and high–alcohol‐drinking (HAD) rats are selectively bred for high alcohol preference, whereas alcohol‐nonpreferring (NP) rats and low–alcohol‐drinking (LAD) rats are bred for low alcohol preference. However, it is unknown whether NE uptake sites in the LC are associated with alcohol preference in AP and HAD rats when compared with their respective control rats, NP and LAD rats. This study was designed to examine this question.Methods: Animals were decapitated and brains were removed, frozen with dry ice powder, and stored in a deep freezer. The LC tissue blocks were cut into 14 μ cryostat sections, collected on glass slides, and incubated with 0.6 nM [3H]‐tomoxetine in 50 mM Tris‐HCl buffer system. For nonspecific binding, 1 μM desipramine was added to the radioactive ligand. Sections were rinsed, quickly dried, and processed for quantitative autoradiography. In addition, galanin content in the LC was also studied.Results: The LC possessed a high density of [3H]‐tomoxetine binding sites. There were fewer tomoxetine binding sites (fmol/mg protein) in the AP rats (433.0 ± 8.1) than in the NP rats (495.6 ± 3.7). HAD rats (386.5 ± 13.2) also possessed fewer tomoxetine binding sites than LAD rats (458.7 ± 10.1). Galanin content in the LC was similar between AP and NP rats and between HAD and LAD rats.Conclusions: Because both AP rats and HAD rats were selectively bred for alcohol preference, the finding of consistently low levels of [3H]‐tomoxetine binding in the LC of these two lines of rats with high alcohol preference suggests that down‐regulation of NE transporters in the LC of AP and HAD rats may be associated with alcohol‐seeking behavior. A possible involvement of the coerulear NE uptake sites in depression is also discussed. Galanin in the LC may not relate to alcohol preference.
Carbohydrate Craving by Alcohol‐Dependent Men During Sobriety: Relationship to Nutrition and Serotonergic Function
Authors: Moorhouse Mona , Loh Elliot , Lockett Donna , Grymala John , Chudzik George , Wilson Allan 
Published: April 2006

Background: Several studies report reduced serotonin (5HT) in alcohol‐dependent subjects. Furthermore, alcohol increases 5HT in animals. Thus, alcohol dependence may be an attempt to self‐medicate reduced 5HT. Relevant to this, reducing 5HT increases carbohydrate intake, and several studies report increased carbohydrate intake in alcohol‐dependent subjects. Like alcohol, carbohydrate increases 5HT. We hypothesized that a subgroup of the alcohol‐dependent population self‐medicates reduced 5HT with alcohol and alternatively with carbohydrate when not drinking.Methods: Three groups were recruited: a high carbohydrate craving alcohol‐dependent group (n= 10), a low carbohydrate craving alcohol‐dependent group (n= 11), and a nonaddicted control group (n= 12). All groups were placed on a high‐carbohydrate, low‐protein diet for 2 days and then a high‐protein, low‐carbohydrate diet for 2 days. The effects of diet on mood, alcohol craving, stress, and 5HT were measured.Results: Although both alcohol‐dependent groups had similar alcohol cravings at baseline, only the carbohydrate‐craving alcohol‐dependent group craved alcohol significantly more when under the stress of the research protocol. The carbohydrate‐craving alcohol‐dependent subjects presented with distinct personality disorders and were uniquely sensitive to the adverse effects of carbohydrate on mood. Diet had a unique effect on 5HT in the high carbohydrate craving alcohol‐dependent group. The results of platelet 5HT uptake demonstrated that the high‐protein, low‐carbohydrate diet significantly increased Km values of high carbohydrate craving alcohol‐dependent subjects, whereas it reduced the Km values of both non‐carbohydrate‐craving alcohol‐dependent subjects and nonaddicted controls.Conclusion: Carbohydrate‐craving alcohol‐dependent subjects are a distinct subgroup of the alcohol‐dependent population.
Rearing Experiences and Stress‐Induced Plasma Cortisol as Early Risk Factors for Excessive Alcohol Consumption in Nonhuman Primates
Authors: Fahlke Claudia , Lorenz Joseph G. , Long Jeffrey , Champoux Maribeth , Suomi Stephen J. , Higley J. Dee 
Published: April 2006

Background: The purpose of this study was to assess the impact of early rearing and stress‐induced rise of plasma cortisol collected during infancy as a biological predictors of adult alcohol consumption in nonhuman primates.Methods: Ninety‐seven female and male rhesus macaques (Macaca mulatta) were investigated. They were reared for their first 6 months of life either without mothers or other adults but with constant access to same‐aged peers (peer‐reared), or as controls with their mothers (mother‐reared). When subjects reached 6 months of age, they underwent a series of four sequential weeks of 4‐day social separations. Blood was drawn 1 and 2 hr after initiation of the 4‐day separation periods, and the plasma was assayed for plasma cortisol concentrations. When the subjects were young adults (approximately 50 months of age), they were tested for voluntary intake of alcohol for 1 hr per day, 4 days a week, during a period of 5 to 7 weeks under normal living conditions.Results: The social separation challenge increased infant plasma cortisol concentrations, with peer‐reared subjects exhibiting higher stress‐induced cortisol concentrations than mother‐reared animals. Subjects that responded to the social separation challenge with high cortisol levels consumed significantly more alcohol per kilogram of body weight as adults than subjects with a low cortisol response to the separation challenge, regardless of rearing condition. In addition, male and peer‐reared subjects consumed significantly more alcohol than female and mother‐reared subjects, respectively.Conclusions: These findings suggest that early rearing experiences, such as adult absence, and high plasma cortisol concentrations early in life after a social separation stressor, are useful psychobiological predictors of future high alcohol consumption among nonhuman primates.
7α‐ and 7β‐Hydroperoxycholest‐5‐en‐3β‐ol in Muscle as Indices of Oxidative Stress: Response to Ethanol Dosage in Rats
Authors: Adachi Junko , Asano Migiwa , Ueno Yasuhiro , Reilly Matthew , Mantle David , Peters Timothy J. , Preedy Victor R. 
Published: April 2006

Background: Alcohol‐induced muscle disease (AIMD) encompasses both acute and chronic lesions, and affected patients exhibit concomitant functional and structural lesions. The pathogenic mechanisms are unknown, although it is possible that defects in the membrane‐lipid domain are involved. Therefore, the effect of acute ethanol on membrane lipid from rat skeletal muscles (control, n= 7; ethanol, n= 7) was investigated.Methods: Soleus and plantaris skeletal muscles were collected 24 hr after a single dose of 75 mmol/kg of ethanol. Lipids were analyzed by high‐performance liquid chromatography with postcolumn chemiluminescence.Results: We found that two cholesterol‐derived hydroperoxides, 7α‐hydroperoxycholest‐5‐en‐3β‐ol (7α‐OOH) and 7β‐hydroperoxycholest‐5‐en‐3β‐ol (7β‐OOH) were present in soleus muscles of control animals (1.29 nmol/g and 3.20 nmol/g, respectively) and in plantaris (1.83 and 5.18 nmol/g, respectively). These hydroperoxides were significantly elevated by acute ethanol, in not only plantaris but also soleus skeletal muscle of rats. In contrast, protein carbonyl concentration, another indicator of oxidative stress, albeit to proteins, was not significantly affected in either soleus or plantaris muscles of ethanol dosed rats. In addition, gas chromatographic study of fatty acid composition from phospholipid of rat muscle showed a significant increase of 18:2 by ethanol in plantaris as well as soleus. Concomitant decreases occurred in the nonessential/essential fatty acid ratios.Conclusions: This is the first report on 7α‐OOH and 7β‐OOH accumulation in rat skeletal muscle, and it seems to reflect greater oxidative stress in the pathology of muscle of rats treated with acute ethanol. Together with the elevation of 18:2, these results signify perturbations in membrane lipids in response to ethanol, which may have important implications for the pathogenesis of alcohol‐induced muscle disorders.