bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Repeated Ethanol Withdrawal on Glutamate Microdialysate in the Hippocampus
Authors: Dahchour Abdelkader , Witte Philippe De 
Published: May 2006

Background: Our previous studies, which identified that ethanol withdrawal is associated with increases in glutamate microdialysate in the nucleus accumbens and reaches a maximum at 12 hr, have now been extended in order to assess whether repeated cycles of chronic ethanol intoxication followed by 12 hr withdrawal periods on three occasions alters glutamate release in the hippocampus of male rats. Methods: In this study, the microdialysis technique has been used with the HPLC and electrochemical detection. Results: During the first cycle of ethanol withdrawal, glutamate content increased significantly 8 hr after withdrawal (198.4%± 89.14%) by comparison with control rats. During the second period of ethanol withdrawal, 1 week after the initial withdrawal episode, glutamate microdialysate content increased significantly 10 hr after withdrawal, but to a much lower degree than in the first episode (179.08 ± 25.68%), by comparison with control rats. During the third cycle of ethanol withdrawal, the concentration of glutamate in the hippocampus microdialysate did not significantly change at either of these time points except at 12 hr when glutamate was significantly decreased by comparison with control rats (52.09 ± 14.38%). Apart from arginine, which was significantly decreased both at the cessation of alcoholization and during the 12 hr of the three withdrawal episodes, none of the other neurotransmitters assayed, aspartate, taurine, alanine, or GABA, showed any significant alteration.Conclusion: These results clearly indicate that elevated glutamate release during the first withdrawal episode is not paralleled in subsequent withdrawal episodes.
Alcohol Inhibition of Cell Adhesion in BMP‐Treated NG108‐15 Cells
Authors: Wilkemeyer Michael F. , Pajerski Mandy , Charness Michael E. 
Published: May 2006

BackgroundThe L1 cell adhesion molecule is expressed as alternatively spliced neuronal and nonneu‐ronal isoforms. We have reported that in transfected fibroblasts, ethanol variably inhibits cell‐cell adhesion mediated by the nonneuronal isoform of human L1. In contrast, ethanol consistently inhibits morphoge‐netic changes and cell‐cell adhesion in NG108‐15 cells treated with OP‐1 (BMP‐7), a powerful inducer of L1 and N‐CAM gene expression.MethodsAll studies were performed by using NG108‐15 cells cultured in serum‐free medium. Cell morphology was assessed by a quantitative assay of cell clustering. Cell adhesion was measured by a short‐term re‐aggregation assay, and isoforms of L1 were characterized by RT‐PCR and sequencing.ResultsWe show that ethanol inhibits the morphogenetic effects of BMP‐2, BMP‐4, BMP‐5, and BMP‐6, each of which increases the expression of L1 and N‐CAM. Pretreatment of NG108‐15 cells with 25‐100 mM ethanol did not induce tolerance to ethanol's inhibition of OP‐1 morphogenesis or cell‐cell adhesion. Ethanol or anti‐L1 Fab fragments partially inhibited cell‐cell adhesion in OP‐1‐treated NG108‐15 cells. The combination of ethanol and Fab fragments did not inhibit cell‐cell adhesion more than Fab fragments alone. As in L1‐transfected fibroblasts, a series of n‐alcohols displayed a cutoff between butanol and pentanol for inhibition of cell‐cell adhesion in OP‐1‐treated NG108‐15 cells. RT‐PCR and direct sequencing revealed that the neuronal isoform was the sole or predominant L1 isoform in OP‐1‐treated NG108‐15 cells.ConclusionsThese data suggest that ethanol inhibits cell‐cell adhesion in OP‐1‐treated NG108‐15 cells by interacting directly or indirectly with the neuronal isoform of L1.
MK‐801‐Induced Locomotor Activity in Long‐Sleep × Short‐Sleep Recombinant Inbred Mouse Strains: Correlational Analysis With Low‐Dose Ethanol and Provisional Quantitative Trait Loci
Authors: Zahniser Nancy R. , Negri Cori A. , Hanania Taleen , Gehle Vaughn M. 
Published: May 2006

BackgroundLaw doses of theN‐methyl‐D‐aspartate receptor (NMDAR) antagonist MK‐801 (dizocilpine) or ethanol increase locomotor activity to a lesser extent in long‐sleep (LS), than in short‐sleep (SS), mice. LS mice also have fewer brain (3H]MK‐801 binding sites than SS mice. In this study, LSXSS recombinant inbred (RI) mice were used to investigate whether different NMDAR densities contribute to differential MK‐801 activation and whether common genes are involved in initial sensitivity to MK‐801‐ and ethanol‐induced activation.MethodsLocomotor activity was measured for 90 min after saline or MK‐801 injection. Quantitative autoradiographic analysis of [3H]MK‐801 binding was used to measure densities of NMDARs in seven brain regions. The ethanol (1–2 gkg) activation scores from Erwin and colleagues (1997) were used for correlational analysis, as was their method for quantitative trait loci (QTL) analysis.ResultsBoth saline and MK‐801 (0.3 mgkg, given intraperitoneally) induced a continuum of locomotor responses across the LSXSS RI strains. There was a 4‐fold range of MK‐801 difference scores (MK‐801 score‐saline baseline), with the RI 9 and RI 4 strains representing low and high responders, respectively. Dose‐response experiments with these two strains confirmed that 0.3 mgkg MK‐801 produced significant activation, similar to previous results with LS and SS mice. However, unlike previous LS/SS results, lower densities of NMDARs were not observed in the RI 9 than in the RI 4 mouse brains. No significant genetic correlations were observed between MK‐801‐induced and ethanol‐induced responses in the LSXSS RI mice. Two provisional MK‐801 activation QTLs were identified (p< 0.01) on chromosomes 11 and 19, neither in common with those mapped for ethanol activation.ConclusionsDifferent densities of brain NMDARs are unlikely to account for the differential activation of LSXSS RI mice by MK‐801. Additionally, in the RI mice either separate sets of genes regulate low dose MK‐801‐ and ethanol‐induced locomotor responses or the overlapping subset of genes controlling these two behaviors is small (≤ 10%).
Genetic Association Between Chronic Ethanol Withdrawal Severity and Acoustic Startle Parameters in WSP and WSR Mice
Authors: Ponomarev Igor , Crabbe John C. 
Published: May 2006

Background: The present study examined the genetic association between chronic ethanol withdrawal severity and acoustic startle response (ASR) in replicated lines of mice selected for high (Withdrawal Seizure‐Prone; WSP) and low (Withdrawal Seizure‐Rent; WSR) susccptihility to handling‐induced convulsions after withdrawal from chronic exposure to ethanol. Any differences on a nonselected (correlated) trait between the opposite‐selected lines is strong evidence for pleiotropic effects of the genes fixed by selection.Methods: Naïve WSP and WSR micc of both replicates were placed in startle chambers and exposed to a series of white noise stimuli of different intensities. In Experiment 1, two parameters [the maximal acoustic startle response (Rmax), and the sound intensity ncccssary to produce 50% of the maximal startle response (dB50)] were obtained from a least‐squares nonlinear regression by fitting data for each subject to a sigmoidal function that best described the relationship betwcen sound intensity and mean ASR. Response hahituation of WSP and WSR mice to a repeated acoustic stimulus of high intensity was examined in Experiment 2.Results: When ASR amplitude was plotted versus sound intensity, the sigmoid intensity‐response curves of both WSP replicates were shifted to the right rclative to the responses of WSR mice, which suggested decreased startle sensitivity in the WSP animals. Statistical analysis showed that naivc WSP mice were less sensitive (higher dB50) to acoustic stimulation than Scizure‐Resistant animals whereas Rmax was similar for both lines. The selected lines also diffcred in their responses to repeated acoustic stimulation, with WSP mice demonstrating grcater habituation.Conclusion: Results of the present study suggest some common genetic mechanisms underlying behavioral responsiveness to acoustic stimulation and severity of ethanol withdrawal.
Executive Functioning in Children With Heavy Prenatal Alcohol Exposure
Authors: Mattson Sarah N. , Goodman Amy M. , Caine Chip , Delis Dean C. , Riley Edward P. 
Published: May 2006

Background: Children with heavy prenatal alcohol exposure have well documented deficits in overall cognitive ability. Recently, attention has turned to the executive function (EF) domain in this population. Until recently, comprehensive measures of EF have not been available within one test battery. This study used a battery of tests to assess four domains of EF in alcohol‐exposed children.Methods: The Delis‐Kaplan Executive Function Scale was used to evaluate EF in 18 children with heavy prenatal alcohol exposure, with and without a diagnosis of fetal alcohol syndrome (FAS), and 10 nonexposed controls. Children ranged in age from 8 to 15 years. Measures from four domains of executive functioning were analyzed: planning ability, cognitive flexibility, selective inhibition, and concept formation and reasoning. Tasks consisted of primary EF measures as well as measures of secondary component skills.Results: Alcohol‐exposed children were deficient on EF measures compared with nonexposed controls. Furthermore, in most cases, children with and without the FAS diagnosis did not differ from one another. These deficits were not entirely explainable by concomitant deficits on component skills. Specific impairments were identified within the domains of planning and response inhibition, with additional deficits in abstract thinking and flexibility.Conclusions: Deficits in executive functioning were observed in alcohol‐exposed children with or without the diagnosis of FAS and in the absence of mental retardation. Performance on these EF tasks provides insight into the cognitive processes driving overall performance and has implications for adaptive and daily functions. These results arc consistent with anecdotal and empirical reports of deficits in behavioral control and with neuroanatomical evidence of volumetric reductions in structures within the frontal‐subcortical system in children with heavy prenatal alcohol exposure.
Altered GABAA‐Benzodiazepine Receptor Number and Pharmacology in the Adult Guinea Pig Cerebral Cortex After Chronic Prenatal Ethanol Exposure
Authors: Bailey Craig D.C. , Brien James F. , Reynolds James N. 
Published: May 2006

Background: The effects of chronic prenatal ethanol exposure on GABAA‐benzodiazepine receptor number and binding pharmacology were examined in the cerebral cortex of the postnatal guinea pig.Methods: [3H]Flunitrazepam binding to GABAA‐benzodiazepine receptors was measured in a cerebral cortical cell membrane preparation obtained at postnatal days 11 (preweaning), 21 (postweaning), and 61 (adulthood). Zolpidem, a GABAA‐benzodiazepine type 1 receptor‐selective ligand, was used in a [3H]flunitrazepam compctition study. 3α‐Hydroxy‐5α‐pregnan‐20‐one (allopregnanolone) potentiation of [3H]muscimol and [3H]flunitrazepam binding, and GABA potentiation of [3H]flunitrazepam binding were measured in these same animals.Results: At postnatal day 61, but not at the younger ages studied, the following was observed: (1) [3H]Flunitrazepam binding exhibited an increased receptor number (Bmax) and decreased affinity (increased KD) in the ethanol‐treated offspring compared with isocaloric‐sucrose (with pair‐feeding) and water‐treated controls; and (2) the relative proportion of GABAA‐benzodiazepine receptors that had high‐affinity binding sites for zolpidem was decreased in the ethanol‐treated offspring by 31% and 38% compared with the isocaloric‐sucrose/pair‐fed and water‐treated controls, respectively. Chronic prenatal ethanol exposure did not alter the efficiency of coupling between GABA, benzodiazepine, and neurosteroid binding sites at any postnatal ages studied.Conclusions: These results suggest that, in the cerebral cortex of the adult guinea pig, chronic prenatal exposure to ethanol results in increased GABAA‐benzodiazepine receptor number, decreased affinity for flunitrazepam, and decreased relative proportion of the GABAA‐benzodiazepine type 1 receptor.
Alcohol Metabolism and Cardiovascular Response in an Alcoholic Patient Homozygous for theALDH2*2Variant Gene Allele
Authors: Chen Yi‐Chyan , Lu Ru‐Band , Peng Giia‐Sheun , Wang Ming‐Fang , Wang Hsu‐Kun , Ko Huei‐Chen , Chang Yue‐Cune , Lu Jang‐Jih , Li Ting‐Kai , Yin Shih‐Jiun 
Published: May 2006

Background: Alcohol metabolism is one of the biological determinants that can influence drinking behavior. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the principal enzymes involved in ethanol metabolism. Allelic variation of theADHandALDHgenes can significantly affect vulnerability for the development of alcoholism. Homozygosity of the variantALDH2*2allele previously was believed to fully protect East Asian populations against the development of alcoholism.Methods: Eighty Han Chinese alcoholics who met DSM‐III‐R criteria for alcohol dependence and 144 nonalcohol‐dependent subjects were recruited and their data combined with data from 340 alcohol‐dependent and 545 nonalcohol‐dependent subjects described in an earlier report (Chen et al., 1999) to assess risk for alcoholism by logistic regression analysis. Genotypes ofADH2, ADH3, andALDH2were determined by polymerase chain reaction and restriction fragment length polymorphism. TheALDH2genotype was confirmed by direct nucleotide sequencing. Blood ethanol concentration was determined by headspace gas chromatography and acetaldehyde concentration by high‐performance liquid chromatography with fluorescence detection of the derivatized product. Cardiovascular hemodynamic parameters were measured by two‐dimensional Doppler echocardiography and sphygmomanometry. Extracranial arterial blood flow was measured by Doppler ultrasonography.Results: An alcohol‐dependent patient was identified to beALDH2*2/*2, ADH2*2/*2, andADH3*1/*2.Following challenge with a moderate oral dose of ethanol (0.5 g/kg of body weight), the patient exhibited peak concentrations for ethanol (55.7 mg/dl) and acetaldehyde (125 μM). During 130 min postingestion, the patient generally displayed similar or even less intense cardiovascular hemodynamic alterations when compared to a previously published study of nonalcoholic individuals withALDH2*2/*2who had received a lower dose of ethanol (0.2 g/kg). Logistic regression analysis of the combinatorial genotypes ofADH2andALDH2in 420 alcohol‐dependent and 689 nonalcohol‐dependent subjects indicated that risk for alcoholism was 100‐fold lower for theADH2*2/*2—ALDH2*2/*2individuals than theADH2*1/*1—ALDH2*1/*1individuals.Conclusions: The gene status ofALDH2*2/*2alone can tremendously but not completely (as thought previously) protect against development of alcohol dependence. Individuals carrying the combinatorial genotype ofADH2*2/*2—ALDH2*2/*2are at the least risk for the disease in East Asians. Physiological tolerance or innate insensitivity to the accumulation of blood acetaldehyde following alcohol ingestion may be crucial for the development of alcoholism in individuals homozygous forALDH2*2.
CYP2E1 Expression in Human Lymphocytes From Various Ethnic Populations
Authors: Raucy Judy L. , Schultz Eric D. , Kearins Margaret C. , Arora Sanjeev , Johnston David E. , Omdahl John L. , Eckmann Lars , Carpenter Susan P. 
Published: May 2006

Background: Monitoring CYP2E1 levels in alcoholic individuals holds inherent appeal because such determinations might indicate individuals at increased risk for alcoholic liver disease. We previously demonstrated that lymphocyte CYP2E1 expression reflects in vivo activity of the hepatic enzyme. Methods: To further validate this approach, the current investigation compared lymphocyte CYP2E1 content and chlorzoxazone pharmacokinetics in 51 alcoholic and nonalcoholic White, Navajo, and Mexican American subjects. After an oral dose of chlorzoxazone, blood samples were collected and lymphocytes isolated. Results: Alcoholics exhibited a 2‐fold clevation in lymphocyte CYP2E1 messenger ribonucleic acid (mRNA) and protein compared to nonalcoholics. Chlorzoxazone clearance rates were 1.9‐fold higher and area under the concentration curve (AUC) values 1.8‐fold lower in alcoholic individuals compared to nonalcoholics. Furthermore, chlorzoxazone clearance rates correlated (r= 0.55, p < 0.01, n= 38) with lymphocyte CYP2E1 mRNA content, and transcript levels further correlated (r= 0.52, p < 0.001, n= 38) with CYP2E1 protein content. To compare phenotype with genotype, restriction fragment length polymorphism analyses on deoxyribonuclcic acid samples were performed to identify polymorphisms in the CYP2E1 gene. No subjects were homozygous for rare alleles c2 or C. Nonetheless, 27% of the Navajos and 15% of the Mexican Americans were heterozygous for the c2 allele. Two White subjects appeared heterozygous (c1/c2) when RsaI was used to characterize CYP2E1 genotype but homozygous (c1/c1) at the PstI locus. Fifteen percent of Mexican American subjects, 20% of Navajo subjects, and 6% of White subjects were heterozygous for the C allele. Neither CD nor c1/c2 genotypes were associated with alcoholism. Conclusions: Human lymphocyte CYP2E1 mRNA levels may be useful predictors of alcohol‐mediated alterations in hepatic CYP2E1 activity. Moreover, ethnicity does not appear to play a major role in the levels of expression of lymphocyte CYP2E1.
Role of Nitric Oxide‐Dependent Pathways in Ethanol‐Induced Anxiolytic Effects in Rats
Authors: Ferreira Vania M.M. , Valenzuela C. Fernando , Morato Gina S. 
Published: May 2006

Background: Nitric oxide (NO) is a neuromodulator and an intercellular and retrograde messenger that mediates several functions in the central nervous system. The effects of ethanol (EtOH) on neuronal NO‐dependent pathways have been the focus of recent research. Most studies have concentrated on the actions of chronic EtOH exposure. In this study, we examined the role of NO‐dependent pathways in the acute actions of EtOH. Methods: We used the elevated plus‐maze test to study the role of NO‐dependent pathways in the behavior of rats treated with acutc EtOH. We tested the effects of 7‐nitroindazole, a reversible competitive inhibitor of nitric oxide synthasc. We also studicd the effects of the cyclic guanylate monophosphate (cGMP) analog, 8‐Bromoguanosine cyclic 3′, 5′‐monophosphate sodium salt, and the NO donors S‐nitroso‐N‐acetylpenicillamine or sodium nitroprusside. Results: When injected by either intraperitoneal (6 mg/kg) or intrahippocampal (20 nmol) routes, 7‐nitroindazole increased the percentage of open arm entries and time spent in open arms for rats injected with EtOH (1.0 g/kg, ip). This dose of EtOH did not produce an anxiolytic effect when administered alone. Additional experiments were performed with a dose of 1.2 g/kg of EtOH (ip), which produced an anxiolytic effcct. Intrahippocampal administration of the cGMP analog, 8‐Bromoguanosine cyclic 3′3′‐monophosphate sodium salt (40 nmol), or the NO donors S‐nitroso‐N‐acetylpenicillamine (20 or 40 nmol) or sodium nitroprusside (20 or 40 nmol) blocked the anxiolytic effect of this dose of EtOH. Conclusions: These results indicate that inhibition of NO‐dependent pathways enhances, whereas stimulation of these pathways decreases, the efficacy of EtOH to produce anxiolytic effects in rats. We postulate that NO‐dependent increases in guanylate cyclase activity and cGMP levels oppose the anxiolytic effects produced by acute EtOH administration.
No Association BetweenDRD2Locus and Alcoholism After Controlling theADHandALDHGenotypes in Chinese Han Population
Authors: Lee Jia‐Fu , Lu Ru‐Band , Ko Huei‐Chen , Chang Fong‐Ming , Yin Shih‐Jiun , Pakstis Andrew J. , Kidd Kenneth K. 
Published: May 2006

Background:Recent studies on the genetics of alcoholism have examined the association between alcoholism and the dopamine D2 receptor locus(DRD2); our study of Chinese Han gave negative results (Lu et al., 1996). The different genotypes at the genes encoding the enzymes involved in alcohol metabolism, class one alcohol dehydrogenase (ADH2 and ADH3) and mitochondrial aldehyde dehydrogenase (ALDH2), have previously been shown to confer different predispositions to the development of alcoholism in Chinese Han males (Thomasson et al., 1991; Chen WJ et al., 1996; Chen CC et al., unpublished data). Therefore, association studies of alcoholism in Chinese Han might be more sensitive if controlled for the genotypes ofADH2, ADH3, and ALDH2, when other loci, such asDRD2, are examined. This study employs such controls to evaluate the evidence for an association between alcoholism andTaqI‐AandTaqI‐Bgenotypes and haplotypes atDRD2in the Chinese Han population.Methods:We studied 213 Chinese Han subjects (128 alcoholics and 85 nonalcoholics) with alcohol dependence defined according to DSM‐III‐R criteria.Results:Significant linkage disequilibrium was observed between theTaqI‐AandTaqI‐Bsites at theDRD2locus, as previously seen in smaller samples, but no significant association was observed between these genetic variants at theDRD2locus and alcoholism in Chinese Han. Several different stratifications byADHandALDH2genotypes were examined; no genotypes or haplotypes atDRD2differ between alcoholics and nonalcoholics except for a small number of nominally significant p‐values which do not constitute significant results given the many tests done, some of which are not independent of one another due to linkage disequilibrium. These tests included considering the high risk (ADH2*1/*1; *l/*2;ADH3*l/*2; *2/*2; and ALDH2*l/*l)and the low risk(ADH2*2/*2;ADH3*1/*1;andALDH2*1/*2; *2/*2)groups of alcoholics, as well as nonalcoholic controls.Conclusions:After stratification by the relevant genotypes ofADH2, ADH3, andALDH2no significant association exists between the genetic variants at theDRD2locus and alcoholism in the Chinese Han population.
Alcohol Effects on Mood, Equilibrium, and Simulated Driving
Authors: Liguori Anthony , D'Agostino Ralph B. , Dworkin Steven I. , Edwards Don , Robinson John H. 
Published: May 2006

Background: The effects of alcohol on simple versus complex psychomotor performance were compared in 18 adults.Methods: Subjects received ethanol doses of 0.0, 0.5, and 0.8 g/kg in a randomized, double‐blind, within‐subject design. Forty minutes after finishing their drinking, the subjects completed a 60‐min battery of tests that included: 1) a sensory organization posturography test (EquiTest); 2) latency to apply the brake after appearance of a barrier in a driving simulator (brake reaction time); 3) visual analog subjective‐effects scales (VAS); 4) the Profile of Mood States (POMS); 5) critical flicker fusion (CFF); and 6) choice reaction time (CRT).Results: Alcohol dose dependently reduced composite equilibrium scores and increased brake reaction time. On the CRT task, total reaction time was significantly increased after the high dose but not the low dose. Alcohol dose dependently increased VAS “dizzy,”“high,” and “drug effect” ratings. The POMS and CFF were not significantly affected by alcohol.Conclusions: These data suggest that an ethanol dose that neither influences certain mood states nor impairs simple psychomotor task performance nonetheless may impair equilibrium and complex psychomotor tasks (e.g., driving).