bluuebunny/crossref_metadata_2025_split huggingface dataset:
Free‐Choice Ethanol Consumption Under the Influence of GABAergic Drugs in Rats
Authors: Schmitt Ulrich , Waldhofer Susanna , Weigelt Tamara , Hiemke Christoph 
Published: April 2006

Background: Neurobiological mechanisms leading from controlled alcohol consumption to addiction are poorly understood. Among multiple neurotransmitters γ‐amino‐butyric acid (GABA) is suggested to play a role. The present investigation studied effects of drugs interacting with the GABAergic system on the motivation of ethanol consumption.Methods: Fifty male PVG/OlaHsd rats were analyzed for free‐choice ethanol drinking behavior without and with pre‐exposure to drugs acting on the GABAergic system. For pretreatment, animals received the benzodiazepine agonists or antagonists diazepam, flumazenil, or Ro15‐4513, or the GABA uptake inhibitor tiagabine via the drinking water for 4 weeks (day −21 until day 7). On day 0, two bottles containing 5% and 12% ethanol were added. On day 7, GABAergic drug exposure was discontinued and drug solutions were replaced by water. Between days 8 and 35, three alcohol deprivation periods of 1 to 3 days were randomly implemented.Results: The animals ingested substantial amounts of ethanol that was differentially affected by the GABAergic drugs. Diazepam increased and flumazenil decreased ethanol consumption significantly by about 30%. Without GABAergic drug pretreatment, a significant alcohol deprivation effect indicated by enhanced ethanol consumption after re‐exposure to alcohol was observed after the third deprivation phase. The deprivation effect was prevented by pretreatment with diazepam or flumazenil, unaffected by Ro15‐4513, and advanced by tiagabine.Conclusions: Modulation of GABAergic neurotransmission affects subsequent ethanol consumption and deprivation effects. Because enhancing of the GABAergic tone by the GABA uptake inhibitor tiagabine or by the benzodiazepine diazepam had different behavioral consequences, it seemed likely that the two drugs induce differential adaptive changes leading to distinct alterations in the motivation to consume alcohol.
Testing Hypothesized Predictors of Change in Conjoint Behavioral Alcoholism Treatment for Men
Authors: McCrady Barbara S. , Hayaki Jumi , Epstein Elizabeth E. , Hirsch Linda S. 
Published: April 2006

Background: The model on which alcohol‐related Behavioral Couples Therapy (ABCT) is based posits three primary domains related to alcohol consumption: individual factors, the quality and nature of the spouse's response to alcohol‐related situations, and the nature and quality of the couple's marital interactions.Methods: This study tested the model underlying ABCT in a sample of 68 male alcoholics and their partners, who completed at least five sessions of a 15‐session outpatient treatment study in which they received ABCT. Couples were assessed at baseline, during treatment, and for 6 months after treatment completion. Stepwise multiple regression was used to test specific predictors derived from the ABCT model.Results: Some support was provided for each component of the ABCT model. Individual drinker variables predicted drinking outcomes, both during and after treatment. Specifically, greater drinking severity and drinking frequency at baseline predicted poorer drinking outcomes. Older client age and more education predicted less frequent but more intense drinking. Spouse coping was related primarily to measures of drinking intensity, rather than drinking frequency. Less intense drinking during treatment was predicted by greater spousal use of problem solving and social support to deal with problems and less use of self‐blame, wishful thinking, and avoidance. After treatment, however, spouse coping had a less consistent relationship to drinking intensity. In the marital domain, drinking during treatment was unrelated to pretreatment marital satisfaction measures. However, in the 6 months after treatment, men's ability to remain abstinent was predicted by the quality of the pretreatment marital relationship, and the intensity of their drinking was predicted by the degree of their marital happiness immediately after treatment.Conclusions: Results provided substantial support for the ABCT model, particularly in relationship to the role of the spouse in affecting heavy drinking.
Concurrent and Discriminant Validity of DSM‐IV Symptoms of Impaired Control Over Alcohol Consumption in Adolescents
Authors: Chung Tammy , Martin Christopher S. 
Published: April 2006

Background: Little research has examined impaired control over alcohol consumption in adolescents. This study examined the concurrent and discriminant validity of two DSM‐IV dependence criteria that reflect impaired control over drinking: “using more or longer than intended” (Larger/Longer) and “persistent desire or unsuccessful efforts to quit or cut down” (Quit/Cut Down).Methods: Adolescent drinkers, ages 13–19 (N= 173), were recruited from addictions treatment (76%) and community sources (24%). A modified SCID that included assessment of alcohol craving and questionnaires measuring dependence severity, attempts to limit drinking, and impulsivity were administered.Results: Larger/Longer had higher prevalence and an earlier onset than Quit/Cut Down, suggesting that the symptoms respectively represent milder and more severe manifestations of impaired control over drinking. Both symptoms were associated with drinking frequency, dependence severity, episodes of passing out, and an independent measure of unsuccessful attempts to limit drinking. Alcohol craving was associated with both Larger/Longer and Quit/Cut Down. Impulsivity was correlated with Larger/Longer but not Quit/Cut Down.Conclusions: Larger/Longer and Quit/Cut Down demonstrated adequate concurrent validity. The two symptoms were distinguished by severity and differential relations with impulsivity, suggesting that Larger/Longer and Quit/Cut Down reflect different types of impaired control over alcohol consumption. Results suggest the need for improved description and scaling of the impaired control construct in adolescents.
Alcohol‐Related Problems, Drug Use, and Male Intimate Partner Violence Severity Among US Couples
Authors: Cunradi Carol B. , Caetano Raul , Schafer John 
Published: April 2006

Background: Particularly for women, level of intimate partner violence (IPV) severity is associated with risk of injury. Previous research suggests that male drinking problems and drug use are key risk factors. Few studies, however, have examined the associations between male and female alcohol problems and drug use and risk of moderate and severe male IPV in general household population samples.Methods: A multiethnic sample of 1615 married and cohabiting couples was obtained from the 1995 National Study of Couples, a cross‐sectional study on alcohol and IPV. We assessed the contribution of past year male and female alcohol‐related problems (i.e., drinking consequences and alcohol‐dependence symptoms) and illicit drug use to the risk of moderate and severe male IPV. A series of generalized multinomial logit models, with adjustment for sociodemographic and psychosocial covariates, was constructed to assess these associations.Results: Female and male alcohol‐related problems and female drug use, were associated with increased risk of moderate and severe male IPV. Contrary to our expectation, male drug use was not associated with elevated risk for either type of male IPV. Compared with couples residing in low‐unemployment neighborhoods, couples residing in high‐unemployment neighborhoods were at greater risk for severe, but not moderate, male IPV.Conclusions: Alcohol‐related problems among men and women and drug use among women, appear to be important correlates of male IPV severity among couples in the general population. These findings can aid in IPV screening efforts, the formulation of prevention strategies, and help inform batterer and victim treatment programs.
Phosphatidylethanol in Rat Organs After Ethanol Exposure
Authors: Aradottir Steina , Lundqvist Christofer , Alling Christer 
Published: April 2006

Background: Phosphatidylethanol (PEth) is an abnormal phospholipid formed in mammalian cells that have been exposed to ethanol. It has been suggested that PEth mediates some of the damaging effects of ethanol on cells. This study was performed to investigate the level of PEth in organs of rats after in vivo alcohol exposure.Methods: Three exposure models were studied: (1) acute, intraperitoneal injection of ethanol (n= 3 × 3); (2) chronic, forced ethanol drinking (n= 6); and (3) chronic, free choice of ethanol (n= 20). PEth was analyzed by high‐performance liquid chromatography after lipid extraction of the organs.Results: One acute injection gave detectable PEth levels in most organs analyzed, with maximal levels reached after 2 hr. The highest levels were reached in intestines, stomach, and lung. No PEth was detected in skeletal muscle, pancreas, or testis. The two exposure models for oral intake of ethanol also gave detectable PEth levels in most organs. The highest levels were reached in stomach, lung, and spleen. PEth was detected in muscle only in animals with heavy total alcohol intake.Conclusions: PEth is formed in most organs of rats exposed to ethanol acutely or chronically. Variations in PEth level and rates of PEth formation and PEth degradation are organ specific.
Interleukin‐4 Treatment Restores Cellular Immunity After Ethanol Exposure and Burn Injury
Authors: Messingham Kelly A. N. , Heinrich Scott A. , Schilling Eric M. , Kovacs Elizabeth J. 
Published: April 2006

Background: Previous studies from this laboratory showed that the suppression of cell‐mediated immunity after the combined injury of ethanol exposure and burn is mediated by increased presence of the proinflammatory cytokine interleukin (IL)‐6. IL‐4 is a T‐helper cell type 2 lymphocyte‐derived cytokine that serves to down‐regulate the inflammatory response. Therefore, the goal of this study was to evaluate the effects of ethanol exposure and burn injury on lymphocyte production of IL‐4 and to determine whether administration of IL‐4 could improve cellular immunity after ethanol exposure and burn injury through modulation of IL‐6 levels.Methods: Mice were subjected to a 15% total body‐surface area burn (or sham) injury 30 min after being given a single dose of alcohol (or saline) designed to achieve a blood alcohol level of 100 mg/dl. Thirty minutes after burn, mice were treated with IL‐4 (or vehicle) and were killed 24 hr later.Results: Lymphocytes from ethanol/burn mice secreted significantly less IL‐4 in comparison to all other groups of mice (p < 0.05). Administration of IL‐4 resulted in a complete restoration of the delayed‐type hypersensitivity (p < 0.01) and splenocyte proliferative responses (p < 0.05) and a significant reduction in circulating and splenic macrophage‐derived IL‐6 (p < 0.05). Addition of IL‐4 (100 or 300 pg/ml) to cultures generated from ethanol/burn and vehicle mice resulted in a complete restoration of splenocyte proliferation and a concomitant attenuation of macrophage IL‐6 production.Conclusions: These studies suggest that the loss of lymphocyte production of IL‐4 after ethanol exposure and burn injury may contribute to the exaggerated production of IL‐6, a known mediator of immune suppression after injury. Moreover, the administration of IL‐4 may be beneficial for patients with injuries that are characterized by a dysregulated inflammatory response.
Mapping of Quantitative Trait Loci Underlying Ethanol Metabolism in BXD Recombinant Inbred Mouse Strains
Authors: Grisel Judith E. , Metten Pamela , Wenger Charlotte D. , Merrill Catherine M. , Crabbe John C. 
Published: April 2006

Background: Genetic factors are well known to play an important role in determining individual differences in the metabolism of ethanol (EtOH), and several specific polymorphic loci have been identified that significantly contribute to the variability of EtOH metabolism in humans. However, these variant genes are either alcohol or aldehyde dehydrogenases, and the identification of new gene products that contribute to variation in alcohol metabolism would be useful.Methods: To identify quantitative trait loci (QTLs), we correlated variation in polymorphic markers with blood EtOH concentration and the rate of EtOH metabolism (β) in C57BL/6J and DBA/2J strains and in 25 of their recombinant inbred strains after 2 and 3 g/kg of EtOH intraperitoneally.Results: A QTL associated with β values for both doses was definitively mapped to the proximal region of chromosome 17, syntenic with human chromosome 6q25–27. Seven to 12 chromosomal regions were provisionally identified for each phenotype; several were associated with 2 or more phenotypes. Each QTL suggests the location of a gene or genes affecting EtOH pharmacokinetics. Candidate genes suggested by these analyses included several whose gene products are known to be induced by EtOH (e.g., superoxide dismutase, glutathione transferase, and cytochrome P450 2E1), as well as several whose gene products have signaling functions likely to contribute to this induction.Conclusions: These studies provide evidence for the existence of genes affecting EtOH metabolism in multiple chromosomal regions. Future studies will be required to identify the chromosome 17 gene product. Use of other genetic populations, such as B6D2F2 crosses, will be required to determine which of the provisional loci represent true and which represent false‐positive associations.
Alcohol Consumption Promotes Body Weight Loss in Melanoma‐Bearing Mice
Authors: Núñnez Nomelí P. , Carter Patrick A. , Meadows Gary G. 
Published: April 2006

Background: Alcohol consumption is an important risk factor for cancer. Little is known about its effects on cancer progression. Previously, we showed that high ethanol consumption inhibited metastasis of B16BL6 melanoma‐bearing mice without affecting primary tumor growth. On the other hand, ethanol‐consuming tumor‐bearing (TE) mice exhibited decreased survival and decreased body weight as compared to water‐drinking, tumor‐bearing (TW) mice. The focus of this study was to determine how alcohol promotes weight loss in melanoma‐bearing mice.Methods: Female, C57BL/6 mice were given water or 20% w/v ethanol in the drinking water for 3 weeks to 6 months before subcutaneous inoculation of 1 × 106 B16BL6 melanoma cells. Mice continued to receive the same fluids. Biochemical parameters were evaluated at various times after tumor inoculation. Body weight, water content, tumor weight and carcass fat content were determined at necropsy.Results: TW mice elicted a modest weight loss. This response was magnified 2‐fold by alcohol consumption. The weight loss in TE mice is not caused by dehydration, decreased energy intake, or loss of skeletal muscle mass. It resulted specifically from loss in body fat. Other alterations associated with the fat loss in TE mice were: (1) decreased glucose, (2) elevated fatty acids, (3) elevated β‐hydroxybutyrate, (4) elevated glucagon, and (5) increased leptin levels in plasma. Body temperature decreased about 2.9°C in TE mice. Metabolic rate increased in TW mice. The fat loss due to alcohol consumption in tumor‐bearing mice was not due to increased metabolic rate.Conclusions: The response elicited by alcohol consumption in tumor‐bearing mice is complex and associated with alterations in metabolism and hormones. These findings suggest that alcohol abuse could be a risk factor for cancer patients because it invokes a strong depletion of body fat. This could facilitate wasting and shorten survival time.
Microanalysis of Ethanol Self‐Administration: Estrous Cycle Phase‐Related Changes in Consumption Patterns
Authors: Ford Matthew M. , Eldridge J. C. , Samson Herman H. 
Published: April 2006

Background: Female rodent and reproductive cycle‐related patterns in ethanol consumption have been identified grossly, but the regulatory processes that underlie these patterns remain to be clarified. The evaluation of consummatory bout dynamics may be useful in determining the effects of a changing endogenous state (ovarian hormone fluctuations) on ethanol consumption patterns. This study assessed the microstructural components of ethanol intake patterns across the estrus cycle.Methods: Cumulative licking of 13 female Long‐Evans rats was recorded during continuous access (22 hr/day) to 10% ethanol and tap water solutions throughout a 10 week period. Drinking bouts were defined as 20 or more successive licks separated by less than a 60 sec pause. Vaginal smears were obtained daily from each rat between 1100 and 1130 hr to assess estrus cycle phase. ANOVAs were conducted to evaluate estrus cycle effects on consumption pattern parameters.Results: Total daily ethanol intakes were unaffected by estrus cycle phase. Ethanol bout frequency was significantly greater during proestrus compared with all other phases, whereas ethanol bout sizes were significantly attenuated during proestrus compared with estrus and diestrus. Experience with ethanol was associated with a significant decline in bout frequency and a significant elevation in bout size across all cycle phases, which indicated that initiation of ethanol self‐administration occurred over time. A significant main effect of hour and a cycle phase by hour interaction were found for the temporal distribution of ethanol lick responses throughout the estrus cycle, and a progressive shift in lick patterns evolved between estrus and the subsequent proestrus.Conclusions: The estrus cycle phase‐related changes in the microstructural components of ethanol intake suggest that female rats experience periods of altered sensitivity to the neurobiological and reinforcing effects of ethanol. Furthermore, these findings implicate cyclical fluctuations in ovarian hormones and other neuromodulators in the regulation of ethanol consumption patterns throughout the estrus cycle of the female rat.
Beer Congener Stimulates Gastrointestinal Motility Via the Muscarinic Acetylcholine Receptors
Authors: Fujii Wataru , Hori Hisako , Yokoo Yoshiaki , Suwa Yoshihide , Nukaya Haruo , Taniyama Kohtaro 
Published: April 2006

Background: Ethanol and alcoholic beverages are known to affect upper gastrointestinal motility in humans. Beer has been reported to accelerate gastric emptying compared with other beverages that contain the same ethanol concentrations. In this study, we investigated the mechanism that underlies the effects of beer congener on gastrointestinal motility.Methods: Gastric emptying activity was measured by means of movement of a semisolid test meal (0.05% phenol red/1.5% methylcellulose) in mice. To elucidate the mechanism for the effect of beer congener on gastrointestinal motility, we conducted receptor binding assays and contraction study by using longitudinal muscle from guinea pig ileum.Results: Beer congener (1 g/kg orally) enhanced gastric emptying of a semisolid meal in mice. The receptor binding assay revealed that beer congener bound to dopamine D2 receptor and 5‐hydroxytryptamine (5‐HT)3 receptor. These IC50 values were more than 5 mg/ml. However, beer congener bound to 5‐HT2 receptor, 5‐HT4 receptor, and muscarinic M3 receptor with IC50 values of 2, 0.9, and 2 mg/ml, respectively. Beer congener (0.05–2 mg/ml) induced the contraction of longitudinal muscle from guinea pig ileum in a dose‐dependent manner. This effect was not affected by either tetrodotoxin (10−6M) or ketanserin (10−7‐10−5M), an antagonist for the 5‐HT2 receptor. On the other hand, 4‐DAMP (10−8−10−5M), an antagonist for the muscarinic M3 receptor, inhibited the contraction of the longitudinal muscle induced by beer congener (2 mg/ml) dose dependently.Conclusions: Beer congener stimulates gastrointestinal motility via the muscarinic M3 receptor.
The Decreased Cellular Expression of Neuropeptide Y Protein in Rat Brain Structures During Ethanol Withdrawal After Chronic Ethanol Exposure
Authors: Roy Adip , Pandey Subhash C. 
Published: April 2006

Background: Neuropeptide Y (NPY) has been implicated in the alcohol‐drinking behaviors of rodents. This study investigated the possible involvement of NPY in the neuroadaptational mechanisms to chronic ethanol exposure and its withdrawal.Methods: Male Sprague‐Dawley rats were treated either with Lieber‐DeCarli ethanol diet or control diet for 15 days, and ethanol‐fed rats were withdrawn for 0 and 24 hr. The protein expression of NPY was determined in cortical, hippocampal, amygdaloid, striatal, and hypothalamic structures by using the gold‐immunolabeling histochemical procedure.Results: It was found that ethanol withdrawal, but not ethanol treatment, produced significant reductions in NPY protein levels in (1) layers IV and V of the frontal and parietal cortex, (2) layer II of the piriform cortex, (3) the central and medial nuclei of the amygdala, and (4) the paraventricular nucleus of the hypothalamus in rat brain. Chronic ethanol exposure and its withdrawal had no effect on the NPY protein levels in layers II, III, and VI of the frontal and parietal cortex or cingulate gyrus, in hippocampal (CA1, CA2, CA3, and dentate gyrus) and striatal (caudate putamen and globus pallidus) structures, or in the ventro‐medial hypothalamus and basolateral amygdala. However, chronic ethanol exposure and its withdrawal produced significant reductions in NPY protein levels in the arcuate nucleus of the hypothalamus and in layers IV and V of the cingulate gyrus.Conclusions: These results suggest that the decreased protein levels of NPY in the central and medial nuclei of the amygdala, as well as in the cortical and hypothalamic structures, during ethanol withdrawal may play an important role in the neuromechanisms of some ethanol withdrawal symptoms.
Attenuated Heart Rate Responses to Public Speaking in Individuals With Alcohol Dependence
Authors: Panknin Tera L. , Dickensheets Stacey L. , Nixon Sara J. , Lovallo William R. 
Published: April 2006

Background: Because individuals with alcohol dependence (AD) have shown blunted cortisol responses to psychological stress, we assessed whether they also show attenuated cardiovascular responses. This study examined the cardiovascular responses of people meeting DSM‐IV criteria for AD to orthostasis and public speaking.Methods: Heart rate (HR), stroke volume, cardiac output, total peripheral resistance, mean arterial pressure, systolic blood pressure, and diastolic blood pressure during orthostasis and public speaking were assessed by use of impedance cardiography and Dinamap blood pressure monitoring in 20 AD subjects abstinent for 21 to 28 days and in 10 age‐matched controls. Orthostasis consisted of standing, whereas public speaking involved preparing and presenting two speeches. Self‐reported mood state was also assessed during the tasks.Results: AD subjects had significantly lower resting BP compared with controls. Cardiovascular responses to orthostasis were similar between groups. AD subjects had attenuated HR during public speaking but reported similar anxiety responses to controls.Conclusions: Comparable cardiovascular responses to orthostasis in controls and AD subjects suggest intact reflex control of circulation. AD subjects had blunted HR responses to public speaking; this is consistent with the attenuated cortisol responses observed in this sample and in previous studies. This suggests a possible alteration in limbic system regulation of hypothalamic and brainstem responses to psychological stress. Cardiovascular responses of AD subjects that are inconsistent with subjective accounts of tension and anxiety suggest a disconnection between perception of threat and resulting physiologic responses in AD subjects.