bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anxiety and Sensitivity to Ethanol and Pentobarbital in Alcohol Withdrawal Seizure‐Prone and Withdrawal Seizure‐Resistant Mice
Authors: Atkins Alison L. , Rustay Nathan R. , Crabbe John C. 
Published: April 2006

Background: Withdrawal Seizure‐Prone (WSP) and Withdrawal Seizure‐Resistant (WSR) mice were selectively bred for high and low handling‐induced convulsions, respectively, after chronic ethanol treatment. Withdrawal severity is one factor that may contribute to the development of alcoholism and/or substance abuse, and anxiety is another. We sought to explore whether these factors are genetically related.Methods: WSP and WSR mice of two replicate pairs of selected lines were tested for anxiety‐related behaviors on the canopy stretched‐attend‐posture apparatus 20 min after intraperitoneal injection of ethanol (2 g/kg, 20% v/v), pentobarbital (20 mg/kg), or an equivalent volume of saline. Dependent measures of anxiety included number of stretched attend postures (SAP) and time spent in the exposed area of the apparatus. Number of line crossings, which measures overall activity, was also scored.Results: WSP mice given saline exhibited more SAP than WSR mice given saline, which indicated greater baseline anxiety. Ethanol and pentobarbital both reduced SAP and increased time spent in the exposed area of the apparatus, which indicated that both drugs exerted an anxiolytic effect. Despite baseline differences in SAP between selected lines, both anxiolytic drugs reduced SAP to similar levels in WSP and WSR mice.Conclusions: These results support the hypothesis that WSP mice are more sensitive than WSR mice to the anxiety‐reducing effects of ethanol and pentobarbital. Some genes that influence this difference are likely to be the same as those that influence ethanol withdrawal severity. Thus, higher basal anxiety and greater genetic sensitivity to anxiolytic drug effects may relate to a greater genetic predisposition to the development of severe alcohol withdrawal signs.
N‐methyl‐d‐aspartate Receptor Responses Are Differentially Modulated by Noncompetitive Receptor Antagonists and Ethanol in Inbred Long‐Sleep and Short‐Sleep Mice: Behavior and Electrophysiology
Authors: Hanania Taleen , Negri Cori A. , Dunwiddie Thomas V. , Zahniser Nancy R. 
Published: April 2006

Background: Short‐sleep (SS) mice exhibit higher locomotor activity than do long‐sleep (LS) mice when injected with low doses of ethanol or the noncompetitive N‐methyl‐D‐aspartate receptor (NMDAR) antagonist MK‐801 (dizocilpine). SS mice also have higher densities of brain NMDARs. However, two strains of LS X SS recombinant inbred (RI) mice also show differential activation to ethanol and MK‐801, but have similar numbers of NMDARs. Here we used inbred LS (ILS) and SS (ISS) mice to investigate further the relationship between NMDARs and sensitivity to the stimulant effects of low doses of ethanol.Methods: Open field activity and spontaneous alternations were measured after saline or drug injection. [3H]MK‐801 binding parameters were determined in hippocampus, cortex, striatum, and nucleus accumbens. Extracellular field excitatory postsynaptic potentials (fEPSPs) were recorded in the CA1 region of hippocampal slices.Results: Systemic injection of either ethanol or MK‐801 increased locomotor activity to a greater extent in ISS mice than in ILS mice. The competitive NMDAR antagonist 2‐carboxypiperazin‐4‐yl‐propyl‐1–1phosphonic acid (±CPP) depressed activity of ILS, but not ISS, mice. No strain differences were observed in spontaneous alternations or in the number or affinity of NMDARs in the brain regions examined. Likewise, the magnitudes of hippocampal NMDAR‐mediated fEPSPs were similar in ILS and ISS mice and were inhibited to the same extent by a competitive NMDAR antagonist. However, both ethanol and the NMDAR NR2B receptor antagonist ifenprodil inhibited the late component of hippocampal NMDAR fEPSPs to a greater extent in ISS, than in ILS, mice.Conclusions: Differential ethanol‐ and MK‐801‐induced behavioral activation in ILS and ISS mice was not associated with differences in NMDAR number. Nonetheless, pharmacological differences in hippocampal NMDAR responsiveness suggest that ISS mice express NMDARs that have a greater sensitivity to noncompetitive, but not competitive, NMDAR antagonists. These differences, which may reflect differences in NMDAR subunit composition, could underlie the differential responsiveness to low doses of ethanol in ILS and ISS mice.
Effects of Vitamin A Deficiency on Rat Liver Alcohol Dehydrogenase Expression and Alcohol Elimination Rate in Rats
Authors: Pinaire Jane , Smith Jennifer R. , Cho Won Kyoo , Crabb David W. 
Published: April 2006

Background: Vitamin A has been suggested to regulate the expression of liver alcohol dehydrogenase (ADH) in humans. There are few studies on the ability of retinoic acid to affect ADH expression in vivo and none on its effects on alcohol metabolic rate.Methods: Male Sprague Dawley® rats were used for isolation of hepatocytes or were rendered vitamin A deficient by feeding a deficient diet for 7 weeks. ADH, retinoic acid receptor β, and retinoid X receptor α protein levels were analyzed by Western blotting. Alcohol elimination rate was determined by following blood alcohol levels after administering a 1.5 g/kg dose of ethanol intraperitoneally.Results: Retinoic acid had no effect on ADH protein in cultured hepatocytes. In the vitamin A deficient rats, retinol was not detectable in serum or liver at the time animals were killed. ADH and retinoid X receptor α protein levels were unchanged in the deficient group compared with a vitamin A sufficient control group, whereas retinoic acid receptor β levels increased 40%. The deficient rats had a reduced volume of distribution of alcohol, but this largely was accounted for by their smaller body size. The alcohol elimination rates were lower in the deficient animals, but this was accounted for by reduced body and liver weights.Conclusions: Severe vitamin A deficiency did not alter liver ADH protein expression or rates of alcohol elimination when expressed per gram of body or liver weight.
Altered Amygdalar CRF Release and Increased Anxiety‐Like Behavior in Sardinian Alcohol‐Preferring Rats: A Microdialysis and Behavioral Study
Authors: Richter Regina M. , Zorrilla Eric P. , Basso Ana Maria , Koob George F. , Weiss Friedbert 
Published: April 2006

Background: Dysregulation of the stress‐regulatory corticotropin‐releasing factor (CRF) system in the central nucleus of the amygdala (CeA) may be a factor in genetically determined alcohol preference.Methods: To test this hypothesis, basal and restraint stress‐induced CRF efflux in the CeA was determined by microdialysis in Sardinian alcohol‐preferring (sP) and nonpreferring (sNP) rats. In addition, differences in anxiety‐like behavior between sP and sNP rats were evaluated by using the elevated plus maze and conditioned defensive burying tests.Results: Basal dialysate CRF levels in the CeA were elevated in the alcohol‐preferring line (sP, 281.2 ± 83.96 pg/ml; sNP, 70.2 ± 16.76 pg/ml;p < 0.05). In contrast, no differences in whole‐tissue CRF content in the CeA were observed (sP, 1143 ± 142 ng/mg protein; sNP, 1181 ± 139 ng/mg protein). Restraint stress elevated CRF dialysate concentrations in both sP and sNP rats. Rats of the sP line exhibited more anxiety‐like behavior than sNP rats in the elevated plus maze but not in the conditioned defensive burying test.Conclusions: The results suggest that ethanol‐preferring sP rats show a dysregulation in basal CRF release within the CeA that may, in turn, heighten ethanol intake and increase susceptibility to anxiogenic stimuli in these animals.
Maintenance Factors of Recovery From Alcohol Dependence in Treated and Untreated Individuals
Authors: Bischof Gallus , Rumpf Hans‐Jürgen , Hapke Ulfert , Meyer Christian , John Ulrich 
Published: April 2006

Background: Research on natural recovery from alcohol dependence has focused mainly on triggering mechanisms of the remission process. Only a few studies have considered maintenance factors of natural recovery.Methods: In the present study, 93 natural remitters and 42 self‐help group participants were compared. Both groups remitted from alcohol dependence according to DSM‐IV criteria. Several alcohol‐related variables and maintenance factors of the remission process were assessed in a personal interview by using standardized questionnaires.Results: Logistic regression analysis that focused on maintenance factors showed that, independent from direct self‐help group context, self‐help group attendees informed more individuals about their former alcohol problems and sought social support more often as a coping strategy to deal with craving. No further group differences could be identified.Conclusions: Self‐help group participants revealed a higher social engagement to maintain their recovery. Besides this major difference, data support the assumption that more commonalities than differences exist within successful recoveries from alcohol dependence, independent of help‐seeking status.
Environmental Transmission of DSM‐IV Substance Use Disorders in Adoptive and Step Families
Authors: Newlin David B. , Miles Donna R. , van den Bree Marianne B. M. , Gupman Anne E. , Pickens Roy W. 
Published: April 2006

Background: One factor contributing to the 3‐ to 5‐fold increase in risk for substance use disorders (SUDs) among children of alcoholics may be the rearing environment. These influences may include availability of substances, modeling of SUDs, inadequate parenting, or other factors. The contribution of parental environmental influences on offspring with SUDs may be estimated independently of genetic influences through assessment of adoptees raised by nonbiological parents.Methods: Relative risk of SUDs was assessed in adult adoptees (N = 442) of alcoholic and nonalcoholic adoptive parents as well as in stepchildren (N = 1859) with alcoholic or nonalcoholic stepfathers who participated in the community‐based National Longitudinal Alcohol Epidemiologic Survey (NLAES).Results: Rearing by an alcoholic adoptive mother was associated with increased DSM‐IV alcohol abuse. Rearing by an alcoholic adoptive father was predictive of adoptees’ illicit drug use, as well as DSM‐IV drug dependence. Rearing by an alcoholic stepfather was predictive of stepchild DSM‐IV alcohol abuse, illicit drug use, and drug dependence, whereas an alcoholic stepmother was associated with increased illicit drug use in the stepchild. Alcoholism in adoptive parents or step parents did not increase risk for offspring DSM‐IV alcohol dependence. In both adoptive and biological families, there was a subadditive interaction of mother by father alcoholism such that the rate of substance abuse when both parents were alcoholic was less than that expected based on the additive effects of each alcoholic parent.Conclusions: Rearing by an alcoholic parent had a greater influence on alcohol abuse by offspring than on alcohol dependence. The increased risk of proband illicit drug use and drug dependence associated with paternal alcoholism suggested nonspecificity of environmental transmission. Both maternal and paternal cultural transmission effects influenced offspring SUDs.
US Low‐Risk Drinking Guidelines: An Examination of Four Alternatives
Authors: Dawson Deborah A. 
Published: April 2006

Background: This study compared four sets of US low‐risk drinking guidelines (two interpretations of the US Dietary Guidelines and two variations of the NIAAA physicians’ guidelines) in terms of adherence and how well they predicted five different alcohol‐related outcomes.Methods: Using data from a nationally representative sample of 17,542 US adults 21 years of age and over who drank 12 or more drinks in the past year, this study assessed the sensitivity, specificity, overall accuracy, positive and negative predictive values, and odds ratios of the various drinking guidelines (specifically, of having exceeded them with different degrees of frequency) as predictors of alcohol dependence, impaired driving, liver disease, peptic ulcer, and hypertension.Results: The proportions of past‐year regular drinkers exceeding the four sets of guidelines varied from 20.9%, whose average intake exceeded the weekly limits, to between 21.0% and 42.7% who exceeded the daily guidelines at least once a week, and to between 69.2% and 94.2% who ever exceeded the daily limits in the year preceding the interview. Sensitivity and odds ratios were highest for the ever exceeding the Dietary Guidelines daily limits, intermediate for ever exceeding the two variations based on the NIAAA physicians’ guidelines, and lowest for exceeding the Dietary Guidelines interpreted as weekly limits. The opposite pattern was observed for specificity and overall predictive accuracy. When frequently exceeding the daily limits was considered, their sensitivity declined but their specificity and positive predictive value increased.Conclusions: If sensitivity and specificity are deemed equally important, the NIAAA physicians’ guidelines incorporating both daily and weekly limits seem to do the best job of balancing these dimensions in the prediction of a variety of alcohol‐related outcomes.
Diastolic Function Impairment in Alcoholics
Authors: Fernández‐Solà Joaquim , Nicolás José‐María , Paré Joan‐Carles , Sacanella Emilio , Fatjó Francesc , Cofán Montserrat , Estruch Ramón 
Published: April 2006

Background: Chronic excessive ethanol consumption exerts a deleterious effect on the myocardium. Although the effects of chronic alcoholism on systolic cardiac function are well known, diastolic involvement has been evaluated only partially. Therefore, we determined the presence of left ventricular diastolic impairment in chronic alcoholics and its relation with simultaneous systolic dysfunction. We also assessed the influence of ethanol consumption in diastolic impairment.Methods: Thirty‐five alcoholics with cardiomyopathy (ejection fraction ≤ 50%) and 77 alcoholics with normal systolic function (ejection fraction > 50%) were evaluated. Assessment of New York Heart Association functional class, history of ethanol intake, technetium‐99m radionuclide angiocardiography, and bidimensional Doppler echocardiography with evaluation of systolic and diastolic left ventricular function were performed.Results: Diastolic function impairment was present in one third of the alcoholics without cardiomyopathy, compared with two thirds of the patients with cardiomyopathy (p < 0.01). A pseudonormalization phenomenon of diastolic function was observed in patients with more advanced systolic dysfunction (ejection fraction < 32%). The deterioration of the diastolic parameters correlated with ethanol consumption, regardless of age (r= 0.44, p < 0.001 for ratio of peak velocity of the transmitral flow in early diastole and peak velocity of atrial contraction flow, with lifetime dose of ethanol).Conclusions: There seems to be a dose‐dependent effect of ethanol on systolic and diastolic heart function. Diastolic function impairment is present in one third of alcoholics with normal systolic function and is even more frequent when systolic dysfunction coexists.
In Vitro Effects of Ethanol Withdrawal and Spermidine on Viability of Hippocampus From Male and Female Rat
Authors: Prendergast Mark A. , Harris Barton R. , Blanchard John A. , Mayer Sveta , Gibson D. Alex , Littleton John M. 
Published: April 2006

Background: Long‐term ethanol dependence results in neuronal adaptation that likely contributes to ethanol withdrawal‐induced central nervous system excitability and, potentially, neurotoxicity. This has been suggested to result, in part, from increased release of or response to endogenous polyamines. Furthermore, it has been reported that neurological difficulties related to ethanol dependence and withdrawal may be more severe in female than in male alcoholics. Thus, we designed this study to examine effects of the polyamine spermidine on neurotoxicity associated with withdrawal from long‐term ethanol exposure by using organotypic hippocampal slice cultures derived from male and female rats.Methods and Results: Twenty‐four hours of withdrawal after continuous 10 day ethanol exposure (100 mM in culture medium) resulted in cytotoxicity in hippocampal slice explants obtained from both sexes. This was most evident in pyramidal cell layers of the CA1 region, and no sex differences were observed in the severity of damage. Exposure of explants from both sexes to the NMDA blocker MK‐801 during ethanol withdrawal significantly reduced this toxicity. In control cultures, exposure to spermidine (100 μM) alone produced significant and similar cytotoxicity in hippocampal explants of male and female rats. Exposure to spermidine (100 μM) during ethanol withdrawal significantly increased cytotoxicity in all regions of explants. In the CA3 region, spermidine‐potentiation of ethanol withdrawal damage was significantly greater in explants from female rats compared with those from male rats.Conclusions: These data demonstrate the presence of significant hippocampal neurotoxicity during withdrawal from long‐term ethanol exposure that is mediated, in part, by overactivation of NMDA receptors. Furthermore, these findings suggest that the central nervous system of females may be more susceptible than that of males to polyamine‐mediated neuronal damage during withdrawal from long‐term ethanol exposure.
Carbonyl Levels in Type I and II Fiber‐Rich Muscles and Their Response to Chronic Ethanol Feeding In Vivo and Hydroxyl and Superoxide Radicals In Vitro
Authors: Koo‐Ng Robin , Falkous Gavin , Reilly Matthew , Peters Timothy J. , Mantle David , Preedy Victor R. 
Published: April 2006

Background: Chronic alcoholic myopathy is characterized by selective reductions in the size of Type II skeletal muscle fibers (i.e., glycolytic, anaerobic fast‐twitch). Type I (i.e., oxidative, aerobic, slow twitch) fibers are relatively resistant. It is possible that reactive oxygen species may preferentially damage the Type II fibers because the concentrations of several antioxidant enzymes are lower in Type II compared with Type I fibers.Methods: To test the hypothesis, we measured protein carbonyl levels in Type I (i.e., soleus) and Type II (i.e., plantaris) fiber‐rich muscles of rats subjected to chronic alcohol dosage with the Lieber‐DeCarli regimen. Muscles were also exposed to hydroxyl or superoxide radicals in vitro.Results: The Type I fiber‐predominant soleus of control animals had less carbonyl than the Type II fiber‐predominant plantaris. In rats that were fed ethanol for 6 weeks, the weights of the plantaris muscle were preferentially reduced but changes in soleus weight did not achieve significance. However, carbonyl levels were not significantly altered in any muscle in response to alcohol feeding. Calculation of the data in terms of total carbonyl per whole muscle showed decreases in both soleus and plantaris at the end of the 6‐week alcohol feeding period. In response to hydroxyl radical (OH.) generation in vitro, protein carbonyl increased substantially in both soleus and plantaris muscles, but more so in the soleus. The increase in carbonyl in control soleus muscles in response to OH. was significantly lower than in soleus muscles from alcohol‐fed animals. The increase in control plantaris muscle was not significantly different from the increase in carbonyl in corresponding muscles from ethanol‐fed rats in response to OH.. In response to superoxide radicals, carbonyl in control soleus increased, an effect similar to that recorded in the soleus from ethanol‐fed rats. In control plantaris, carbonyl increased in response to superoxide radicals, an effect not significantly different to the increase in plantaris from alcohol‐fed rats.Conclusions: Using increased carbonyl concentrations as an indicator of muscle damage by reactive oxygen species, we concluded (1) there is no evidence of enhanced reactive oxygen species‐induced damage to mixed muscle proteins in either Type I or Type II muscles in response to alcohol feeding; (2) Type II muscles have a greater capacity than Type I muscles to protect against damage (as indicated by carbonyl formation) by both hydroxyl and superoxide radicals in vitro; (3) alcohol reduces the capacity of Type I muscle to resist hydroxyl radical‐induced protein damage, a mechanism that may arise through impairment of other antioxidant systems or other process not yet elucidated.
Individual Differences Predictive of Drinking to Manage Anxiety Among Non‐Problem Drinkers With Panic Disorder
Authors: Kushner Matt G. , Abrams Kenneth , Thuras Paul , Hanson Karen L. 
Published: April 2006

Background: Alcohol problems co‐occur with anxiety disorders at a rate that far exceeds chance (“comorbidity”). One view suggests that risk for developing a comorbid alcohol use disorder is increased when alcohol is used routinely to cope with anxiety symptoms (“self‐medication”). Indicating that this view is overly broad, however, the literature suggests that only a subgroup of anxiety‐disordered individuals tend to drink to manage their symptoms. Therefore, we set out to identify psychological characteristics that might mark those for whom drinking to cope with anxiety is most likely. Our survey of the literature identified several possibilities, including anxiety‐related personality traits (anxiety sensitivity, self‐consciousness and Trait Anxiety); higher‐order personality dimensions (Harm Avoidance, Reward Dependence, and Novelty Seeking); and, finally, alcohol outcome expectancies (specifically, those related to tension‐reducing effects from alcohol).Methods: In a sample of nonproblem drinkers with panic disorder, we regressed predictor variables on several alcohol use measures, including drinking aimed at the control of anxiety symptoms (“self‐medication”).Results: Although each variable related positively to a self‐medicating style of drinking, expectancies for tension reduction from alcohol use accounted for about twice as much variance as did the other predictors. With simultaneous entry in a step‐wise regression analysis, only tension‐reduction alcohol outcome expectancies and the Harm Avoidance personality dimension were retained as significant predictors.Conclusions: Findings suggest that development of a self‐medicating style of drinking among individuals with panic disorder is predicated, in part, on specific psychological characteristics of the individual. Alcohol outcome expectancies emerged as the single most important predictor of drinking behavior in this anxiety‐disordered sample.