bluuebunny/crossref_metadata_2025_split huggingface dataset:
Executive Functioning Early in Abstinence From Alcohol
Authors: Zinn Sandra , Stein Roy , Swartzwelder H Scott 
Published: September 2004

Background:Executive dysfunction is among the cognitive impairments that may persist after abstinence in alcohol‐dependent persons. The type(s) and extent of executive dysfunction early in abstinence have not been well characterized, but they may have important implications for the evolution of behavioral treatment strategies.Methods:To determine which aspects of executive functioning were impaired in early abstinence, we administered memory and executive function tests to veterans who successively presented for treatment at an outpatient substance abuse clinic. We then compared the neuropsychological performance of these recovering alcoholics (n= 27) with that of age‐matched primary care outpatients (n= 18). We also examined group differences in self‐evaluation of cognitive decline and evaluated associations between drinking history and cognitive impairment in the index group.Results:We found that the normal and alcohol‐dependent groups differed on abstract reasoning, memory discrimination, and effectiveness on timed tasks. Patients in the alcohol‐dependent sample were also more likely to perceive themselves as cognitively impaired. It is interesting to note that the duration of alcohol use did not relate to neuropsychological test performance, but recent quantity consumed and days of sobriety were associated with nonverbal abstract reasoning ability.Conclusions:Executive functions are impaired early in abstinence and should, therefore, be taken into account when early behavioral treatments are being developed.
A Review of Genetic, Biological, Pharmacological, and Clinical Factors That Affect Carbohydrate‐Deficient Transferrin Levels
Authors: Fleming Michael F. , Anton Raymond F. , Spies Claudia D. 
Published: September 2004

Background: Carbohydrate‐deficient transferrin (CDT) is an alcohol biomarker recently approved by the U.S. Food and Drug Administration. This test is increasingly being used to detect and monitor alcohol use in a variety of health care, legal, and industrial settings. The goal of this study is to review the genetic, biological, pharmacological, and clinical factors that may affect CDT levels.Methods: A review of the literature identified 95 research articles that met the authors’ criteria and reported potential interactions of a variety of factors on percent and total CDT levels. The review established 12 categories of variables that may affect CDT levels. These categories include (1) alcohol use, (2) genetic factors, (3) race, (4) gender, (5) age, (6) liver disease, (7) iron levels, (8) tobacco use, (9) medication such as estrogen and anticonvulsants, (10) metabolic factors such as body mass index and total body water, (11) chronic medical conditions such as rheumatoid arthritis, and (12) surgical patients.Results: There is evidence that %CDT levels are affected by alcohol use, end‐stage liver disease, and genetic variants. In addition to these three factors, total CDT levels (CDTect) are also affected by factors that raise transferrin levels such as iron deficiency, chronic illnesses, and menopausal status. Other potential factors such as tobacco and age appear to be confounded by alcohol use. The roles of female gender, low body mass index, chronic inflammatory diseases, and medication on CDT levels require further study. False negatives are associated with female gender, episodic lower level alcohol use, and acute trauma with blood loss.Conclusions: This review suggests that a number of factors are associated with false‐positive CDTect and %CDT levels. CDT offers great promise to assist physicians in the care of patients to detect and monitor heavy alcohol use.
Differential Effects of Ethanol on γ‐Aminobutyric Acid‐A Receptor‐Mediated Synaptic Currents in Congenic Strains of Inbred Long and Short‐Sleep Mice
Authors: Proctor William R. , Wu Peter H. , Bennett Beth , Johnson Thomas E. 
Published: September 2004

Background: Ethanol enhances γ‐aminobutyric acid (GABA)A receptor‐mediated responses in the brain, and this enhancement is greater in a mouse line behaviorally more sensitive to ethanol (long sleep) than in a line (short sleep) behaviorally less ethanol sensitive (assayed by loss of righting; sleep time). Quantitative trait locus (QTL) analysis of inbred long sleep (ILS) and inbred short sleep (ISS) phenotypes revealed four chromosomal regions (Lore1, Lore2, Lore4, and Lore5) that together account for approximately 50% of ethanol‐induced sleep‐time variance. Congenic strains were generated, each of which is homozygous for one of four ISS Lore QTLs on the ILS background. These congenic mouse strains are ideally suited for asking which QTL regions might correlate with other phenotypes that differ between ILS and ISS mice. Here we used the congenics to investigate altered GABAA responses to ethanol.Methods: Evoked GABAA receptor‐mediated inhibitory postsynaptic currents (IPSCs) were measured by whole‐cell voltage‐clamp recording procedures in CA1 pyramidal neurons in hippocampal brain slices.Results: GABAA IPSC responses in hippocampal brain slices from ILS mice were significantly enhanced by 80 mM ethanol, whereas those from ISS mice were not affected. ILS.Lore2S and ILS.Lore5S congenic strains were significantly enhanced by 80 mM ethanol, similar to the background (control) ILS mice. However, ethanol had no significant effect on GABAA responses in ILS.Lore1S and ILS.Lore4S congenic mice, similar to the ISS mice, thus reflecting the influence of ISS alleles on the ILS phenotype.Conclusions: Our results suggest that alleles located in the Lore1 and Lore4 QTL regions confer ethanol sensitivity of GABAA receptor‐mediated IPSCs. Thus, for these QTLs, GABAA IPSCs may represent an endophenotype of sedative/hypnotic sensitivity to ethanol. Although the Lore2 and Lore5 QTL regions have a significant effect on sleep time, they do not play a significant role in the differential ethanol enhancement of GABAA IPSCs between ILS and ISS mice.
Acute Ethanol‐Induced Adenosine Diphosphate Ribosylation Regulates the Functional Activity of Rat Striatal Pertussis Toxin–Sensitive G Proteins
Authors: Dar M Saeed , Meng Z ‐H. 
Published: September 2004

Background: We demonstrated previously that striatal adenosine modulates ethanol‐induced motor incoordination (EIMI) via adenosine A1 receptors coupled to pertussis toxin (PT)‐sensitive G protein and adenylyl cyclase‐cyclic adenosine monophosphate (cAMP). Additionally, intrastriatal (IST) PT antagonizes EIMI and its potentiation by the adenosine A1 agonist N6‐cyclohexyladenosine; it also inhibits cAMP concentration.Methods: Guide cannulas were stereotaxically implanted for IST pretreatment with PT followed 5 days later by IST of N6‐cyclohexyladenosine and intraperitoneal ethanol. The adenosine diphosphate (ADP) ribosylation reaction involved PT‐catalyzed [32P]nicotinamide adenine dinucleotide (NAD) labeling of rat striatal membranes. Antagonism of EIMI (Rotorod method) after IST microinfusion of PT was investigated to determine whether it was due to a decrease in the functional activity of G proteins due to ADP ribosylation of the Giα subunit caused it.Results: Striatal membranes from IST PT (0.5 μg)–treated animals exhibited significantly attenuated (up to 90%) in vitro ADP ribosylation with [32P]NAD. Striatal membranes from animals injected with ethanol (1.5 g/kg intraperitoneally) exhibited statistically significant increase (11%) in in vitro ADP ribosylation. Similarly, ethanol (50 mM) added to striatal membranes from untreated animals produced significant stimulation of in vitro ADP ribosylation. The decrease in the functional activity of G proteins due to ADP ribosylation of the Giα subunit after IST PT was functionally correlated with marked attenuation in EIMI, as observed previously. This finding suggests a blockade of functional activity of PT‐sensitive striatal Gi/Go proteins (i.e., fewer available sites for labeled NAD incorporation). The in vivo ethanol results indicate that it must have caused an increase in the ribosylation capacity of Giα in vivo (i.e., increased Gi activity). Increased ADP ribosylation by in vitro ethanol increases Gi/Go activity, consistent with EIMI, as previously reported.Conclusions: The results provide biochemical evidence of an ethanol‐induced increase in ADP ribosylation of Giα causing a decrease in the functional activity of G proteins coupled via Gi/Go to adenylyl cyclase‐cAMP. These results confirm the previously observed antagonism of EIMI by PT (IST).
Trends in Drinking Among Americans Age 18 and Younger: 1975–2002
Authors: Faden Vivian B. , Fay Michael P. 
Published: September 2004

Background: Although changes over time in the prevalence of drinking by youth under 18 have been previously reported, we present results based on data from multiple surveys, using recently developed software for trend analyses. In this study, we applied joinpoint statistical methodology to three national data sets to analyze trends in drinking by youth, age 18 and under, for the period 1975 to 2002.Methods: Information was obtained from three national data sets, Monitoring the Future for the years 1975 to 2002, the Youth Risk Behavior Survey for the years 1991 to 2001, and the National Household Survey on Drug Abuse for 1979, 1985, and 1991 to 2001.Approximately 80,000 persons between 12 and 18 were included in the most recent survey years. The alcohol consumption measures examined over time were any use of alcohol, consumption of five or more drinks on one occasion, and daily consumption.Results: Alcohol consumption by 8th, 10th and 12th graders decreased substantially since the 1970s according to joinpoint trend analyses. It remains disturbingly high, however, according to data from three national surveys (e.g., 12.4% of 8th and 28.6% of 12th graders drinking five or more drinks in a row in the past 2 weeks), although prevalence rates have been relatively stable for the last 5 to 10 years.Conclusions: Since the early 1990s, rates of drinking by youth under 18 remained relatively stable according to the Youth Risk Behavior Survey and National Household Survey on Drug Abuse and moved up and then down according to Monitoring the Future, underscoring the need for continued surveillance and enhanced understanding of this long‐standing problem.
Ethanol Operant Self‐Administration in Rats Is Regulated by Adenosine A2 Receptors
Authors: Arolfo Maria Pia , Yao Lina , Gordon Adrienne S. , Diamond Ivan , Janak Patricia H. 
Published: September 2004

Background: Recent findings suggest that adenosine is involved in the neural and behavioral effects of ethanol (EtOH). Studies in neural cell culture show that EtOH, via activation of adenosine A2 receptors, triggers cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling and CRE (cAMP regulatory element)‐mediated gene expression and that this effect is blocked by inhibiting G‐protein βγ subunits. Recently, we reported that expression of a βγ inhibitor in the nucleus accumbens (NAc) reduces EtOH drinking in rats. The NAc expresses high levels of the adenosine A2A receptor in GABAergic medium spiny neurons. If the reinforcing effects of EtOH are mediated through an A2 activation of cAMP/PKA signaling via βγ, then A2 receptor blockade should attenuate EtOH consumption. Here we tested this hypothesis. Because adenosine A2 and dopamine D2 receptors are coexpressed in neurons of the NAc, we compared the effects of A2 blockade with those of D2 receptor blockade.Methods: Male Long‐Evans rats were trained to self‐administer 10% EtOH in daily 30‐min sessions with an active and an inactive lever. Separate groups of rats were given the D2 antagonist eticlopride (0.005, 0.007, and 0.01 mg/kg), the A2 antagonist 3,7‐dimethyl‐1‐propargylxanthine (DMPX; 1, 3, 5, 7, 10, and 20 mg/kg), and the A1 antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX; 0.125, 0.25, and 0.5 mg/kg) by systemic injection.Results: Eticlopride dose‐dependently reduced EtOH drinking. DMPX showed a bimodal effect: 10 and 20 mg/kg decreased, but 1 mg/kg increased, EtOH consumption. DPCPX was without effect.Conclusions: In support of our hypothesis, the A2 antagonist DMPX attenuated EtOH self‐administration. Low doses of the A2 antagonist enhanced EtOH drinking, consistent with the possibility that rats increase EtOH self‐administration to overcome partial A2 blockade. The D2 antagonist eticlopride also decreased EtOH self‐administration. These data provide the first evidence that pharmacological modulation of adenosine A2 receptors can regulate EtOH consumption in rats.
Does an Energy Drink Modify the Effects of Alcohol in a Maximal Effort Test?
Authors: Ferreira Sionaldo Eduardo , de Mello Marco Túlio , Rossi Marcio Vinicius , Souza‐Formigoni Maria Lucia O. 
Published: September 2004

Background: There are popular reports on the combined use of alcohol and energy drinks (such as Red Bull® and similar beverages, which contain caffeine, taurine, carbohydrates, etc.) to reduce the depressant effects of alcohol on central nervous system, but no controlled studies have been performed. The main purpose of this study was to verify the effects of alcohol, and alcohol combined with energy drink, on the performance of volunteers in a maximal effort test (cycle ergometer) and also on physiological indicators (oxygen uptake, ventilatory threshold, respiratory exchange rate, heart rate, and blood pressure), biochemical variables (glucose, lactate, insulin, cortisol, ACTH, dopamine, noradrenaline, and adrenaline), and blood alcohol levels.Methods: Fourteen healthy subjects completed a double‐blind protocol made up of four sessions: control (water), alcohol (1.0 g/kg), energy drink (3.57 ml/kg Red Bull®), and alcohol + energy drink, each 1 week apart. The effort test began 60 min after drug or control ingestion, and the dependent variables were measured until 60 min after the test.Results: Heart rate at the ventilatory threshold was higher in the alcohol and alcohol + energy drink sessions in comparison with control and energy drink sessions. Although in comparison to the control session, the peak oxygen uptake was 5.0% smaller after alcohol ingestion, 1.4% smaller after energy drink, and 2.7% smaller after the combined ingestion, no significant differences were detected. Lactate levels (30 min after drug ingestion, 30 and 60 min after the effort test) and noradrenaline levels (30 min after the effort test) were higher in the alcohol and alcohol + energy drink sessions compared with the control session.Conclusions: The performance in the maximal effort test observed after alcohol + energy drink ingestion was similar to that observed after alcohol only. No significant differences between alcohol and alcohol + energy drink were detected in the physiological and biochemical parameters analyzed. Our findings suggest that energy drinks, at least in the tested doses, did not improve performance or reduce alterations induced by acute alcohol ingestion.
Serum Levels of Tissue Polypeptide Specific Antigen Are Correlated With Hepatocyte Cytokeratin Expression in Alcoholic Liver Disease
Authors: Gonzalez‐Quintela A , Mella C , Abdulkader I , Perez L F. , Campos J , Otero E , Forteza J 
Published: September 2004

Background: Serum levels of the tumor marker tissue polypeptide specific antigen (TPS, cytokeratin 18 fragments) are increased in patients with alcoholic liver disease, particularly in cases of alcoholic hepatitis. Mallory bodies, characteristic of alcoholic hepatitis, are cytokeratin 8 and 18 aggregates. The study was aimed at investigating the possible relationship of serum TPS levels with hepatocyte cytokeratin expression in patients with alcoholic liver disease.Methods: Twenty‐four patients with alcoholic liver disease were studied. Immunohistochemical staining for cytokeratins 8 and 18 was performed in liver specimens by means of CAM 5.2 monoclonal antibody. The number of hepatocytes containing CAM 5.2‐reactive cytokeratin inclusions was compared with serum TPS levels.Main Results and Conclusions: The vast majority of alcoholics (95%) showed increased (>100 units/liter) serum TPS levels. Serum TPS levels were significantly correlated with the number of hepatocyte cytokeratin inclusions. Serum TPS levels can predict hepatocyte cytokeratin expression in patients with alcoholic liver disease.
Chronic Ethanol‐Induced Subtype‐ and Subregion‐Specific Decrease in the mRNA Expression of Metabotropic Glutamate Receptors in Rat Hippocampus
Authors: Simonyi Agnes , Christian Michael R. , Sun Albert Y. , Sun Grace Y. 
Published: September 2004

Background: Chronic ethanol consumption is known to induce adaptive changes in the hippocampal glutamatergic transmission and alter NMDA receptor binding and subunit expression. Metabotropic glutamate (mGlu) receptors have been shown to function as modulators of neuronal excitability and can fine tune glutamatergic transmission. This study was aimed to determine whether chronic ethanol treatment could change the messenger RNA (mRNA) expression of mGlu receptors in the hippocampus.Methods: Male Sprague Dawley® rats were fed a Lieber‐DeCarli liquid diet with 5% (w/v) ethanol or isocaloric amount of maltose for 2 months. Quantitative in situ hybridization was carried out using coronal brain sections through the hippocampus.Results: The results revealed decreases in mRNA expression of several mGlu receptors in different subregions of the hippocampus. In the dentate gyrus, mGlu3 and mGlu5 receptor mRNA levels were significantly lower in the ethanol‐treated rats than in the control rats. In the CA3 region, the mRNA expression of mGlu1, mGlu5, and mGlu7 receptors showed substantial decreases after ethanol exposure. The mGlu7 receptor mRNA levels were also declined in the CA1 region and the polymorph layer of the dentate gyrus. No changes were found in mRNA expression of mGlu2, mGlu4, and mGlu8 receptors.Conclusions: Considering the involvement of hippocampal mGlu receptors in learning and memory processes as well as in neurotoxicity and seizure production, the reduced expression of these receptors might contribute to ethanol withdrawal‐induced seizures and also may play a role in cognitive deficits and brain damage caused by long‐term ethanol consumption.
Implicit Strategy Affects Learning in Children With Heavy Prenatal Alcohol Exposure
Authors: Roebuck‐Spencer Tresa M. , Mattson Sarah N. 
Published: September 2004

Background: Learning and memory deficits are commonly reported in children with heavy prenatal alcohol exposure. Our recent work suggested that children with heavy prenatal alcohol exposure retained information as well as controls on a verbal learning test but not on a test of nonverbal learning and memory. To better understand the cause of this differential pattern of performance, the current study re‐analyzed data from our previous study to determine if the presence of an implicit learning strategy may account, at least in part, for the finding of spared retention.Methods: The current study examined verbal learning and memory abilities in 35 children with Fetal Alcohol Spectrum Disorders (FASD) and 34 nonexposed controls (CON) matched for age (9–16 years), sex, ethnicity, handedness, and socioeconomic status. Groups were compared on two measures of verbal learning, one with an implicit strategy (California Verbal Learning Test–Children's Version; CVLT‐C) and one without (Verbal Learning subtest of the Wide Range Assessment of Memory and Learning; VL‐WRAML).Results: Children with FASD learned less information overall than children in the CON group. Both groups learned a greater percentage of information and reached a learning plateau earlier on the CVLT‐C compared with the VL‐WRAML. Groups also showed comparable rates of retention after a delay on the CVLT‐C. In contrast, on the VL‐WRAML, children with FASD showed poorer retention rates than children in the CON group. Interestingly, children with FASD did not differ from children in the CON group on CVLT‐C semantic clustering scores for learning trials 1 through 3, and greater utilization of semantic clustering was correlated with better learning and memory performance in both groups. This overall pattern of results was not related to overall intellectual level.Conclusions: The finding of spared retention of verbal information on the CVLT‐C in our earlier studies may be related to test characteristics of the CVLT‐C rather than a finding of spared verbal retention per se, given that spared retention was not found on a separate test of verbal learning and memory without an implicit learning strategy. These results suggest that the use of an implicit strategy positively affected the ability of alcohol‐exposed children to learn and retain new verbal information.
Increased P3 Amplitudes Induced by Alcohol‐Related Pictures in Patients With Alcohol Dependence
Authors: Namkoong Kee , Lee Eun , Lee Choong Heon , Lee Byung Ook , An Suk Kyoon 
Published: September 2004

Background:Alcohol craving, a key element in alcohol dependence, is recognized as being a kind of motivational or emotional state. It is meaningful in research and clinical practice involving alcohol dependence to explore ways of measuring alcohol craving. The aim of this study was to measure the P3 event‐related potentials induced by alcohol‐related pictures in patients with alcohol dependence; these potentials are considered to constitute a neuronal correlate of alcohol craving.Methods:On the basis of our previous study, six alcohol‐related pictures and six neutral pictures were chosen as the visual stimuli. Each set of stimuli consisted of alcohol‐related or neutral pictures as the target stimuli and same‐sized checkerboards as the nontarget stimuli. The stimuli were presented by using the oddball paradigm for 300 msec, with an interstimulus interval of 1000 msec, in 12 controls and 16 abstinent patients with alcohol dependence. Each electroencephalography session consisted of three blocks: a practice block, a neutral block, and an alcohol‐craving block.Results:The amplitudes of P3 elicited by the alcohol‐related pictures were significantly larger than those elicited by the neutral pictures in the patients with alcohol dependence, whereas there was no significant difference according to the stimuli in the P3 amplitudes of controls. Repeated‐measures ANOVA on the amplitudes of P3 revealed that there was a significant interaction effect of block by subject group.Conclusions:These results suggest that event‐related potentials can be used as a neuronal correlate of alcohol craving in alcohol‐dependent patients. Future investigations will be needed to assess the frequency of relapse in the patients included in this study, to elucidate the meaning of the observed results with regard to the therapeutic outcomes.