bluuebunny/crossref_metadata_2025_split huggingface dataset:
Saccadic Eye Movements Are Associated With a Family History of Alcoholism at Baseline and After Exposure to Alcohol
Authors: Blekher Tanya , Ramchandani Vijay A. , Flury Leah , Foroud Tatiana , Kareken David , Yee Robert D. , Li Ting‐Kai , O'Connor Sean 
Published: April 2006

Objective To evaluate the influence of family history of alcoholism (FHA) on the response of saccadic eye movements to alcohol.Method Saccadic performance was evaluated in 54 healthy adult subjects with a FHA (family history–positive) and 49 controls (family history–negative). Alcohol and placebo sessions were presented in counterbalanced order. Alcohol was administered intravenously to achieve and maintain a target breath alcohol concentration of 60 mg/100 ml (60%) for 160 min in each subject. During each session, saccadic eye movement testing was performed at baseline (before infusion of alcohol) and twice during the steady‐state target breath alcohol concentration. The saccadic testing elicited visually guided saccades (VGS) and antisaccades (AS). Saccadic latency and velocity and the percentage of AS errors were quantified and analyzed using multivariate analysis of variance.Results The family history–positive and family history–negative groups showed an overall difference at baseline in AS and VGS latencies and velocities in the alcohol and placebo sessions (p= 0.006). Alcohol delayed saccades such that AS and VGS latencies increased (p= 0.0001) and slowed the execution of saccades such that peak velocities decreased (p= 0.0002). The percentage of AS errors decreased after alcohol administration, but no significant effect of alcohol (alcohol versus placebo session) was observed (p= 0.1). Latency of AS saccades demonstrated a significant overall FHA effect (p= 0.02) and a significant interaction between FHA and response to alcohol over time (p= 0.02).Conclusions Differences in operational characteristics of the saccadic control system are associated with FHA in adult social drinkers, both at baseline and when the brain is exposed to ethanol at 60 mg/100 ml.
Prenatal Alcohol Exposure Predicts Continued Deficits in Offspring Size at 14 Years of Age
Authors: Day N. L. , Leech S. L. , Richardson G. A. , Cornelius M. D. , Robles N. , Larkby C. 
Published: April 2006

Background Growth deficits are among the cardinal features for the diagnosis of fetal alcohol syndrome. Growth deficits have also been noted among those who were exposed to alcohol prenatally but who do not have fetal alcohol syndrome. Few studies have observed subjects past early and middle childhood, however, to evaluate the longer‐term effects of prenatal alcohol exposure on growth in adolescence. This is a report of the effects of alcohol exposure during gestation on the size of the offspring at 14 years of age.Methods Women were recruited in their fourth prenatal month. These women were interviewed in the fourth and seventh months of pregnancy and at delivery. The women and their children were seen when the offspring were 14 years of age.Results Growth deficits associated with prenatal alcohol exposure were identified among the offspring at 14 years of age. Weight, height, head circumference, and skinfold thickness continued to be significantly affected by prenatal alcohol exposure after controlling for other significant predictors of size. These effects exhibited a dose‐response pattern, and significant effects were found at levels below one drink per day. For example, first trimester alcohol exposure predicted weights of 152 lbs for the offspring of abstainers, 149 lbs for the offspring of light drinkers (>0 and <0.2 drinks per day), 143 lbs for the offspring of moderate drinkers (>0.2 and <0.89 drinks per day), and 136 lbs for the offspring of heavy drinkers (>0.89 drinks per day).Conclusions Prenatal alcohol exposure continues to affect size at age 14 years in this cohort of children followed since their fourth month of gestation.
Genetic Dissection of Quantitative Trait Loci Specifying Sedative/Hypnotic Sensitivity to Ethanol: Mapping With Interval‐Specific Congenic Recombinant Lines
Authors: Bennett Beth , Beeson Mary , Gordon Lena , Carosone‐Link Phyllis , Johnson Thomas E. 
Published: April 2006

Background Linkage studies alone do not produce sufficient resolution to narrow the location of a quantitative trait locus (QTL) to a small‐enough chromosomal region for gene identification. One solution to this problem is to use interval‐specific congenic recombinant (ISCR) lines to narrow the chromosomal interval known to contain the QTL. In previous work, we mapped four QTLs for differential ethanol sensitivity in the inbred long‐sleep (ILS) and inbred short‐sleep (ISS) strains and generated reciprocal congenic strains in which each full QTL interval from ILS was bred onto the ISS background and vice versa.Methods ISCR lines were derived by identifying mice carrying recombination events in the congenic interval during backcrossing of the ISS.ILS. Lore congenics to ISS. Recombinant mice were backcrossed to ISS, and progeny carrying the ISCR chromosome were identified and tested to determine whether the ISCR region carried the donor Lore QTL.Results We developed multiple ISCR lines for each Lore QTL, in which the QTL interval was broken into a number of smaller intervals. For all four QTLs, we reduced the size of the interval, in one case to 3.7 cM.Conclusions Use of ISCR lines can narrow each Lore candidate region to a few centimorgans. Such an interval size is conducive to brute‐force approaches to identify candidate genes, entailing bioinformatics, gene expression, and DNA sequencing strategies.
Effects of Ethanol Exposure on Subsequent Acquisition and Extinction of Ethanol Self‐Administration and Expression of Alcohol‐Seeking Behavior in Adult Alcohol‐Preferring (P) Rats: I. Periadolescent Exposure
Authors: Rodd‐Henricks Zachary A. , Bell Richard L. , Kuc Kelly A. , Murphy James M. , McBride William J. , Lumeng Lawrence , Li Ting‐Kai 
Published: April 2006

Background The current study examined the effects of ethanol (EtOH) drinking during periadolescence on the subsequent acquisition and extinction of operant self‐administration of EtOH and expression of alcohol‐seeking behavior in adult alcohol‐preferring (P) rats to test the hypothesis that alcohol drinking during periadolescence produces enduring alterations that enhance the reinforcing properties of EtOH.Methods Periadolescent female P rats were given 24 hr free‐choice access to 15% (v/v) EtOH starting at postnatal day (PND) 30 and ending on PND 60 or were similarly housed and received water only. On PND 75, without any prior training, periadolescent alcohol‐drinking and periadolescent alcohol‐naïve rats were placed in standard two‐lever (15% EtOH and water) chambers to examine acquisition of EtOH self‐administration with a fixed ratio (FR) 1 schedule of reinforcement. After the acquisition phase and after stable responding was established on an FR5 for EtOH and FR1 for water, P rats underwent extinction training for both EtOH and water rewards. After extinction training and a 2 week home cage period, rats were returned to the operant chambers in the absence of reward for seven consecutive sessions (Pavlovian spontaneous recovery). After this testing period, animals were maintained in their home cage for a week before being returned to the operant chambers and allowed to respond for EtOH and water (reacquisition).Results Compared with periadolescent alcohol‐naïve rats, periadolescent alcohol‐drinking rats acquired EtOH responding sooner (i.e., in the first acquisition session), displayed a greater resistance to extinguish EtOH responding (i.e., higher levels of responding in sessions 4–6), had higher responding for more sessions on the EtOH lever in the absence of reward after a prolonged home cage rest period, and had a more prolonged elevated level of EtOH responding during reacquisition (four sessions versus one session).Conclusions Overall, the results suggest that periadolescent EtOH drinking by P rats produced long‐lasting alterations in the reinforcing effects of alcohol, which increased the likelihood that alcohol drinking would be initiated in adulthood, decreased the likelihood that once adult alcohol drinking began it could be extinguished easily, and increased the potential for relapse.
Ethanol‐ and Sucrose‐Reinforced Appetitive and Consummatory Responding in HAD1, HAD2, and P Rats
Authors: Czachowski Cristine L. , Samson Herman H. 
Published: April 2006

Introduction Ethanol‐preferring (P) rats and high‐alcohol‐drinking (HAD1 and HAD2) rats have been selectively bred to consume greater amounts of ethanol than nonselected rat strains. These three rat lines also show increased levels of responding for ethanol in operant paradigms that assess a combined appetitive/consummatory response.Methods The present experiment used a model of reinforced responding that procedurally separates the appetitive, or seeking, response requirement from consummatory responding to compare seeking and intake responding in P and HAD rats. Subjects (n= 7 or 8 per group) were trained to make 25 lever‐press responses, which were followed by 20 min of access to a sipper tube spout containing either 10% ethanol (10E) or (in separate groups of subjects) 3% sucrose (3S). After training, a single nonreinforced session was conducted to assess the limit to appetitive responding under extinction conditions. After this single nonreinforced session, three successive across‐session breakpoint determinations were made for 10E and 3S by increasing the response requirement over days until subjects failed to complete the requirement. A final extinction session was then conducted.Results Appetitive responding during both the nonreinforced and breakpoint sessions indicated that P rats made significantly more responses overall than HAD rats in both the ethanol and sucrose groups. P rats also consumed more sucrose than HAD rats, with no differences in ethanol consumption between the lines (1.0–1.5 g/kg/20 min). Appetitive responding in the HAD rats in the ethanol groups was comparable to that reported previously for nonselected Long‐Evans rats.Conclusions These findings indicate that appetitive and consummatory processes are distinct and that P rats have an increased tendency to both seek and drink ethanol and sucrose solutions, making this selected line useful when modeling both “craving” and “loss of control” related behaviors involved in excessive alcohol consumption.
Alcohol Suppresses Insulin‐Like Growth Factor‐1 Gene Expression in Prepubertal Transgenic Female Mice Overexpressing the Bovine Growth Hormone Gene
Authors: Srivastava Vinod K. , Dearth Robert K. , Hiney Jill K. , Chandrashekar Varadaraj , Mattison Julie A. , Bartke Andrzej , Dees W. Les 
Published: April 2006

Background Alcohol (ALC) delays puberty in female rats and alters the development of a normal menstrual pattern in rhesus monkeys. These actions are associated with depressed serum levels of growth hormone (GH), luteinizing hormone and insulin‐like growth factor‐1 (IGF‐1). The mechanism of this ALC‐induced depression in IGF‐1 is not known, however, could be due to depressed GH and, possibly, to an alteration in the hepatic GH receptor. To assess whether ALC has a direct action at the liver, we used a transgenic mouse model that overexpresses GH, allowing assessment of potential direct actions of ALC on the level of either the GH receptor or the IGF‐1–synthesizing machinery within the hepatocyte.Methods One group of transgenic mice was fed a liquid diet containing ALC. The second group was pair‐fed the companion isocaloric control liquid diet. The third group of transgenic mice was fed Lab Chow and water. The fourth group consisted of normal (nontransgenic) littermates fed Lab Chow and water. Animals received their respective diets for 5 days. Mice were killed during their late juvenile stage of development, and tissues and blood collected and frozen.Results The ALC‐fed transgenic mice showed a decrease (p < 0.01) in hepatic IGF‐1a and IGF‐1b messenger RNA levels compared with transgenic controls, and this paralleled a decrease (p < 0.01) in serum IGF‐1. ALC did not alter the circulating levels of bovine GH held constant by the promotor and did not alter mouse GH receptor protein levels as analyzed by Western blotting.Conclusions Using this transgenic animal model that maintains circulating GH in the presence of ALC, we found that the ability of ALC to suppress prepubertal Igf1 gene expression can also occur independently of any alterations in the level of circulating GH. This direct effect on the hepatocyte is a postreceptor event because the GH receptor protein levels were not altered by ALC exposure.
β‐Endorphin Modulation of Lymphocyte Proliferation: Effects of Ethanol
Authors: Boyadjieva Nadka I. , Dokur Madhavi , Advis Juan P. , Meadows Gary G. , Sarkar Dipak K. 
Published: April 2006

Background We have previously shown that alcohol suppresses the natural killer (NK) cell activity of splenic lymphocytes partly by reducing the secretion of opioid peptide β‐endorphin (β‐EP) and its positive influence on NK‐cell cytolytic activity in rats. The inhibition of NK‐cell cytolytic activity was also associated with a reduced number of NK cells after chronic ethanol administration. Hence, the possibility arises that chronic ethanol may alter NK cell proliferation, survival, or both. In this study, we investigated whether ethanol treatment for 1 to 4 weeks reduces the proliferation of other lymphocyte subsets and whether β‐EP regulates ethanol's effect on lymphocyte proliferation.Methods Male rats were ad libitum–fed rat chow, pair‐fed with isocaloric liquid diet, or fed with ethanol‐containing liquid diet for 1, 2, 3, or 4 weeks. Groups of these rats were infused with β‐EP with or without the δ‐receptor antagonist naltrindol into the paraventricular nucleus of the hypothalamus. Splenocytes were isolated and used for flow cytometric analysis of the changes in the number of various lymphocyte subsets. Lymphocyte proliferation was determined by mitogen stimulation assays.Results Ethanol consumption resulted in a reduction of the number of CD161+ NK cells, CD3+ T lymphocytes, CD4+ T‐helper cells, and CD8a+ cytotoxic T cells in a time‐dependent fashion. Alcohol consumption also suppressed the proliferative response of lymphocyte subsets to concanavalin A, phytohemagglutinin, and lipopolysaccharide. β‐EP promoted the lymphocytes’ proliferative response to mitogens, whereas naltrindol blocked the effects of the opioid. Chronic alcohol consumption reduced the proliferative response of lymphocytes to β‐EP.Conclusions These results suggest that chronic alcohol administration reduces immune function partly by decreasing the opioid‐regulated mitogen‐stimulated proliferation of lymphocyte subsets.
A Proline‐Threonine Substitution in Codon 351 of ADH1C Is Common in Native Americans
Authors: Osier Michael V. , Pakstis Andrew J. , Goldman David , Edenberg Howard J. , Kidd Judith R. , Kidd Kenneth K. 
Published: April 2006

Background The alcohol dehydrogenase (ADH) genes have been repeatedly associated with protection against alcoholism. Until now, only four protein coding variants have been identified (ADH1C Arg271Gln, Ile349Val, ADH1B Arg47His, and Arg369Cys), and only two of these (ADH1C Ile349Val and ADH1B Arg47His) have been routinely tested in association studies with alcoholism.Methods The new ADH1C*351Thr allele was identified by direct sequencing of DNA samples that gave different typing results for the ADH1C Ile349Val polymorphism with different typing protocols.Results A new coding variant has been identified at codon 351 of ADH1C. This allele is found in most Native American populations that we have studied with allele frequencies of the new ADH1C*351Thr allele as high as 26%. Only two instances of this allele have been seen in a large survey of African and Eurasian populations.Conclusions The changes in charge, size, and rotational mobility caused by this amino acid substitution should be significant. Because this new variant codes for a new enzyme form in Native Americans, the kinetics of this enzyme should be studied and considered in studies of the role of ADH1C in the protection against alcoholism in Native Americans.
Binge Drinking in Jewish and Non‐Jewish White College Students
Authors: Luczak Susan E. , Shea Shoshana H. , Carr Lucinda G. , Li Ting‐Kai , Wall Tamara L. 
Published: April 2006

Background In the United States, religious commitment, as measured by service attendance, has an inverse relationship with alcohol consumption, heavy use, and problem use. This association, however, has not been found consistently in Jewish Americans. The present study examined the relationship between religious variables and binge drinking in Jewish and non‐Jewish white college students. In addition, the association among genetic, cultural, and religious variables and binge drinking was examined in the Jewish sample alone.Methods Participants were 132 Jewish and 147 non‐Jewish white college students. All participants completed the Time‐Line Follow‐Back, had blood drawn for genotyping at the alcohol dehydrogenase locus ADH2, and reported their religious affiliation and the number of religious services attended in the past year. Jewish subjects also completed the Jewish Identity Scale.Results As hypothesized, more frequent religious service attendance related to lower rates of binge drinking in non‐Jews but was not related to binge drinking in Jews. Within the Jewish sample, individuals who were religiously affiliated had approximately one third the risk of binge drinking as those who were secularly affiliated, but identification with Jewish culture was not related to binge drinking. In the total sample, individuals who possessed a variant alcohol dehydrogenase allele ADH2*2 were approximately half as likely to binge drink as those who did not possess this allele.Conclusions These results are consistent with previous studies that find an inverse relationship between religious service attendance and heavy alcohol use in Christian but not Jewish college students. Findings within the Jewish sample support theories that suggest religious, not just cultural, Jewish affiliation relates to lower levels of alcohol behavior. More research is needed to identify additional factors, including other religious, cultural, genetic, and biological influences, that protect Jewish Americans from heavy drinking.
Long‐Term Effects of and Physiological Responses to Nitrous Oxide Gas Treatment During Alcohol Withdrawal: A Double‐Blind, Placebo‐Controlled Trial
Authors: Alho Hannu , Methuen Taina , Paloheimo Markku , Strid Nuria , Seppä Kaija , Tiainen Juha , Salaspuro Mikko , Roine Risto 
Published: April 2006

Background Nitrous oxide gas (N2O) has been proposed to be effective in the treatment of the alcohol withdrawal syndrome (AWS). This has not been proved, however, in studies performed according to good clinical practice guidelines. Moreover, previous studies have not measured end tidal N2O concentrations or physiologic responses during N2O treatment. We have recently reported that in a double‐blind, randomized, controlled setting, N2O was not superior to placebo in relieving AWS symptoms. In this previous study, we did not find significant differences between the treatments either in the Clinical Institute Withdrawal Assessment of Alcohol scores or in the total use of benzodiazepines (diazepam and temazepam). The aim of the present study was to characterize other effects and side effects of the N2O treatment using several objective measures and to study the possible long‐term efficacy of the treatment.Methods A total of 105 inpatients who had AWS and were admitted to the A‐Clinic detoxification center were included in the study. The subjects were randomly assigned to one of the following three treatments: (1) N2O/oxygen (from 30 to 70% in oxygen), (2) air/oxygen (30%/70%), and (3) medical (normal) air. During the single 45‐min treatment period, end‐tidal N2O, carbon dioxide, and oxygen concentrations were measured. The physiologic responses were studied by measuring heart rate, blood pressure, pulse oximetric saturation, frontal muscle electromyographic activity, and plethysmographic pulse amplitude. Long‐term effects were studied by measuring craving with the Obsessive‐Compulsive Drinking Scale; severity of dependency with Severity of Alcohol Dependence Data; and liver enzymes with aspartate aminotransferase, alanine aminotransferase, and γ‐glutamyltransferase 3 and 6 months after the treatment.Results Patients in the N2O group demonstrated significantly higher facial muscle electromyographic activity and higher pulse amplitude than the air‐treated subjects. Self‐reported side effects between the gas treatments, however, did not differ between the groups. Regarding long‐term effects of the treatments, there were no differences between the groups.Conclusions Contrary to previously published data, N2O treatment did not decrease craving or liver enzymes during the 6‐month follow‐up. At the concentration used, N2O treatment produced signs of arousal instead of strong sedation.
Reciprocal Congenics Defining Individual Quantitative Trait Loci for Sedative/Hypnotic Sensitivity to Ethanol
Authors: Bennett B. , Beeson M. , Gordon L. , Johnson T. E. 
Published: April 2006

Background: We have identified four major genes or quantitative trait loci (QTLs) that determine duration of loss of righting reflex (LORR), induced by sedative doses of ethanol:Lore1, Lore2, Lore4, and Lore5. Together these genes explain more than 50% of the phenotypic variance for sensitivity to the sedative/hypnotic effects of ethanol between the Inbred Long Sleep (ILS) and Inbred Short Sleep (ISS) strains of mice. The derivation of these strains is reviewed here.Methods: Each QTL has been bred onto the opposite background (ILS or ISS) through 10 rounds of backcrossing by using QTL‐marker‐assisted counter selection to produce reciprocal congenic strains. Mice were genotyped for markers that flanked each of the QTLs. Selection for the donor at the desired QTL, and against donor markers at the other four QTLs, allowed rapid fixation of the genetic background. Phenotypic assessment in the ISS‐recipient congenic strains was conducted throughout the backcross.Results: By the N5 generation, phenotypic assessments failed to detect significant effects in some sublines; these sublines were discarded and positive lines split to create new replicate sublines. In the N10, all sublines retained the phenotypic difference between heterozygotes and ISS homozygotes; however, the expected additive effect was not found in the Lore1 congenics. On the ILS background, each Lore was captured, as shown by the expected differential LORR. Two strains on the ILS background, and one on the ISS, exhibited the differential effect on blood ethanol concentration associated with the donor strain.Conclusions: Congenic strains represent an important resource for confirmation of previously identified QTLs, for identification and mapping of additional phenotypes, and for exclusion of candidate genes. QTL‐marker‐assisted selection rapidly stabilized the genetic background within four generations (based on phenotypic assessments); however, phenotypic selection during the backcrossing to generate congenic strains did not contribute to the successful capture of the ISS QTLs.