bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impairment in Eyeblink Classical Conditioning in Adult Rats Exposed to Ethanol as Neonates
Authors: Green John T. , Rogers Ronald F. , Goodlett Charles R. , Steinmetz Joseph E. 
Published: April 2006

Background: Eyeblink classical conditioning is a learning task that engages well‐defined neural circuitry in the cerebellum and brainstem. Binge‐like exposure to alcohol during the neonatal brain growth spurt in rats produces neurotoxic effects on both the cerebellum and the brainstem. The precise localization of the neural substrates of eyeblink conditioning makes it an ideal task to study functional disruptions in the cerebellum and brainstem caused by early exposure to alcohol. The purpose of this study was to determine whether impairments in eyeblink conditioning caused by neonatal binge exposure to alcohol persist into adulthood, indicative of long‐lasting abnormalities in cerebellar and brainstem function.Methods: Group Ethanol received alcohol doses of 5.25 g/kg/day via intragastric intubation on postnatal days 4–9. Group Sham Intubated underwent the intragastric intubation procedures on postnatal days 4–9 but did not receive any infusions. Group Nonintubated did not receive any intubations. When all rats were at least 3 months old, they were tested in either paired or unpaired eyeblink conditioning.Results: Group Ethanol showed impaired eyeblink conditioning and some abnormalities in conditioned response timing. Control groups did not differ from each other.Conclusions: The present data indicate that early exposure to alcohol has long‐term effects on eyeblink conditioning, perhaps through enduring effects associated with alcohol‐induced loss of Purkinje cells of the cerebellum.
Carbohydrate‐Deficient Transferrin (CDT) and HDL Cholesterol (HDL) Are Highly Correlated in Male Alcohol Dependent Patients
Authors: Szegedi Armin , Müller Matthias J. , Himmerich Hubertus , Anghelescu Ion , Wetzel Hermann 
Published: April 2006

Background: Serum levels of total HDL cholesterol (HDL) are reportedly influenced by recent alcohol intake. We examined the correlation between HDL cholesterol and widely used markers of excessive alcohol intake, such as carbohydrate‐deficient transferrin (CDT), γ‐glutamyl‐transferase (GGT), or mean corpuscular volume of erythrocytes (MCV), of which CDT is thought to be the most specific.Methods: Several serological markers [i.e., CDT, GGT, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), MCV, and HDL] were determined in 100 actively drinking male patients with alcohol dependence (DSM‐IV) and in 27 non‐alcohol‐dependent controls, according to routine procedures. Spearman‘s rank correlation coefficients were calculated.Results: We found a highly significant positive correlation between HDL and CDT (rs= 0.55;p < 0.0005) in patients, but not in controls (rs= 0.13;p= 0.51). HDL was also positively correlated with GGT, ALAT, ASAT, and MCV only in patients.Conclusions: HDL cholesterol, as a widely determined parameter, may represent a useful routine marker for recent excessive alcohol intake. High HDL cholesterol levels should alert clinicians to investigate a patient's recent pattern of alcohol consumption.
Effects of Acute, Moderate Ethanol Consumption on Human Platelet Aggregation in Platelet‐Rich Plasma and Whole Blood
Authors: Zhang Qing‐Hui , Das Kabita , Siddiqui Shahid , Myers Adam K. 
Published: April 2006

Background: Platelet‐inhibitory effects of alcohol potentially contribute to the reduced risk of coronary heart disease associated with moderate drinking. However, few studies have directly examined the effects of acute consumption of a moderate dose of alcohol on aggregation of platelets from healthy human subjects. In the present study, we examined those effects, with the use of multiple platelet agonists and two aggregation measurement techniques, as part of an ongoing series of studies that evaluate the actions of ethanol on platelet function.Methods: Human subjects consumed alcohol at a dose equivalent to one drink (0.25 ml/kg) or two drinks (0.5 ml/kg). One hour after ingestion, anticoagulated blood was collected and agonist‐induced aggregation of platelets was measured in both whole blood and in platelet‐rich plasma.Results: Inhibition of aggregation by ethanol consumption was observed in whole blood (measured as maximum change in impedance) and reached statistical significance (p < 0.05) in the 0.5 ml/kg alcohol group for two collagen concentrations (0.625 and 1.25 μg/ml) as well as for the highest concentration of adenosine diphosphate tested (p < 0.05). Inhibition was 15.4%, 22.6%, and 10.5%, respectively, for these three situations. In platelet‐rich plasma, after consumption of 0.5 ml/kg ethanol, aggregation (measured as maximum change in optical density) in response to 1.25 μg/ml collagen was significantly inhibited (p < 0.05); no other significant inhibition was observed at either dose of alcohol in any other cases with platelet‐rich plasma. In comparison of male and female subjects, there was a statistically significant difference (p < 0.05) in the degree of inhibition by ethanol consumption (0.5 ml/kg) of whole‐blood platelet aggregation induced by collagen, whereby female aggregation was inhibited to a greater extent than male.Conclusions: This study shows that alcohol, at physiologically relevant doses, below those investigated in most previous human studies, has a dose‐dependent inhibitory effect on platelet aggregation. Such an effect could potentially contribute to the beneficial effects of alcohol consumption against coronary artery disease. The inhibitory action is most readily measured with whole‐blood platelet aggregometry, with the use of collagen as the agonist. This observation is consistent with the view that alcohol reduces platelet sensitivity to thrombotic stimuli by inhibition of arachidonic acid release and, therefore, subsequent thromboxane synthesis.
Formation of Malondialdehyde Adducts in Livers of Rats Exposed to Ethanol: Role in Ethanol‐Mediated Inhibition of Cytochrome c Oxidase
Authors: Chen Juanjuan , Petersen Dennis R. , Schenker Steven , Henderson George I. 
Published: April 2006

Background: Previous studies in our laboratory demonstrated that short‐term ethanol consumption by maternal rats increased the hepatic levels of 4‐hydroxynonenal (HNE) in both the adult and the fetus. Additionally, HNE inhibited cytochrome c oxidase (COX) by forming adducts with the enzyme subunits. The present study examined modification of COX by another major aldehydic lipid peroxidation product, malondialdehyde (MDA), and its role in COX inhibition by ethanol.Methods and Results: It is demonstrated in vitro that MDA inhibits the activity of purified COX while forming adducts with the enzyme. Compared with HNE, MDA is a more potent inhibitor of COX. Overnight incubation at room temperature caused an 80% decrease in COX activity by MDA versus a 67% decrease by HNE. MDA produced marked inhibition of COX activity at physiologically relevant concentrations, e.g., 43% inhibition at 10 μM. Although our previous studies documented that HNE formed adducts primarily with subunit IV of COX via histidine residues, the current report showed that MDA forms adducts with both subunit IV and subunit V via lysine residues. Furthermore, both aldehydes induce carbonyl formation in subunit IV. The in vivo role of MDA in the impairment of COX by ethanol is assessed in both adult and fetal liver after maternal ethanol consumption.Conclusions: The results showed that: (1) there are significant increases in MDA levels in liver homogenate as well as mitochondria in both adult and fetal livers after ethanol exposure; (2) these MDA levels are in the nanomole/mg protein range, in contrast to picomole/mg protein range of HNE in identical setting; and (3) ethanol‐induced production of MDA is accompanied by enhanced formation of MDA adducts with COX. These findings suggest that MDA may play at least as equally an important role as HNE in ethanol‐induced inhibition of COX.
Pattern of Motor and Cognitive Deficits in Detoxified Alcoholic Men
Authors: Sullivan E. V. , Rosenbloom M. J. , Pfefferbaum A. 
Published: April 2006

Background: Chronic excessive consumption of alcohol produces marked deficits in cognitive and motor abilities, although not all functions are affected to the same extent. Furthermore, although the occurrence of neuropsychological deficits in recently detoxified alcoholics is firmly established, the relative severity of these deficits, the specific neural systems that underlie the deficits, and their relationship to age and alcohol consumption variables either are less established or have proven elusive altogether.Methods: We administered an extensive battery of neuropsychological tests, chosen for their known sensitivity to brain lesions in specific locations, to 71 recently (1 month) detoxified alcoholic men and 74 healthy controls who spanned the adult age range. Test scores were standardized to the controls for age and grouped a priori into composites that reflected performance in six functional domains: executive functions, short‐term memory, upper limb motor ability, declarative memory, visuospatial abilities, and gait and balance. Analogous verbal and nonverbal materials and left‐ and right‐hand upper limb motor tasks were used to test whether alcohol‐related deficits were greater for left or right hemisphere.Results: Compared with controls, the alcoholics were impaired on executive functions, visuospatial abilities, and gait and balance even after we accounted for group differences in estimated premorbid IQ and education. Within the alcoholic group, the most salient deficits were in gait and balance and visuospatial abilities. No consistent lateralized deficit was observed across the four domains tested. Unlike the cognitive composites, the upper limb motor ability and gait and balance composites both showed increasing vulnerability to age, with an independent contribution to the gait and balance dysfunction from the amount of alcohol consumed over a lifetime.Conclusions: The pattern of functional deficits implicates at least two principal neural systems: the cerebellar‐frontal system and the corticocortical system between the prefrontal and parietal cortices. In addition, age and amount of alcohol consumption were better predictors of motor than cognitive impairments.
Blunted Stress Cortisol Response in Abstinent Alcoholic and Polysubstance‐Abusing Men
Authors: Lovallo William R. , Dickensheets Stacey L. , Myers Dean A. , Thomas Terrie L. , Nixon Sara Jo 
Published: April 2006

Background: This study tested cortisol responses to a psychological stressor in controls (CT) versus patients who were diagnosed as alcohol dependent (AD) or alcohol and stimulant dependent (ADSD) by DSM‐IV criteria and who were abstinent for 3 to 4 weeks from alcohol and illicit drugs. Alcohol increases cortisol secretion acutely and during withdrawal. However, there is little information about abnormalities of hypothalamic‐pituitary‐adrenocortical (HPA) reactivity in recovering alcoholics.Methods: Accordingly, we tested HPA function in the laboratory between 7:00 and 9:30 AM on control versus stress days. Stress consisted of a 20‐min public speaking challenge with preparation and delivery of two short speeches, ostensibly evaluated for quality of delivery, whereas control involved relaxing for the same period. Cortisol was measured in saliva collected at baseline, stress or control, and recovery period, and also at home at 9:00 PM on one of the two days.Results: The three groups did not differ in diurnal patterns of cortisol secretion on the rest day and 9:00 PM sample, which indicated that AD and ADSD patients had intact diurnal HPA regulation at rest. During speech stress, the CT subjects showed the expected cortisol increase (p < 0.0001), whereas neither AD nor ADSD patients responded significantly. Cortisol values were not accounted for by covariates such as depression, posttraumatic stress disorder, glucose metabolism, or anthropometric or demographic characteristics.Conclusions: The apparent stress hyporesponsiveness of the AD and ADSD patients suggests a persistent disruption of HPA function, perhaps due to incomplete recovery from prior abuse, or to a preexisting alteration in neural systems that regulate HPA responses to stress.
Reliability and Validity of the Alcohol Use Disorders Identification Test (AUDIT) Imbedded Within a General Health Risk Screening Questionnaire: Results of a Survey in 332 Primary Care Patients
Authors: Daeppen Jean‐Bernard , Yersin Bertrand , Landry Ulrika , Pécoud Alain , Decrey Hedi 
Published: April 2006

Background: Self‐administered, general health risk screening questionnaires that are administered while patients wait in the doctor's office may be a reasonable and timesaving approach to address the requirements of preventive medicine in a typical 10‐min medical visit. The psychometric characteristics of the Alcohol Use Disorders Identification Test (AUDIT) incorporated within a health questionnaire (H‐AUDIT) have not been examined.Methods: The reliability and validity of the self‐administered AUDIT were compared between the H‐AUDIT and the AUDIT used as a single scale (S‐AUDIT) in 332 primary care patients.Results: No major demographic or alcohol use characteristics were found between the 166 subjects who completed the H‐AUDIT and the 166 individuals who completed the S‐AUDIT. The test‐retest reliability of the 166 subjects who completed the H‐AUDIT [estimated by Spearman correlation coefficient at a 6‐week interval (0.88), internal consistency (total correlation coefficients for all items ranged from 0.38 to 0.69; Cronbach α index 0.85), and the sensitivity and specificity of the H‐AUDIT were used to identify at‐risk drinkers’ areas under receiver operating characteristic (0.77) and alcohol‐dependent subjects’ areas under receiver operating characteristic (0.89)] was similar to the same measurements obtained with the 166 individuals who completed the S‐AUDIT.Conclusions: The AUDIT incorporated in a health risk screening questionnaire is a reliable and valid self‐administered instrument to identify at‐risk drinkers and alcohol‐dependent individuals in primary care settings.
Ethanol Modulation of γ‐Aminobutyric Acid (GABA)‐Mediated Inhibition of Cerebellar Purkinje Neurons: Relationship to GABAb Receptor Input
Authors: Yang Xiaohong , Criswell Hugh E. , Breese George R. 
Published: April 2006

Background: Electrophysiological recording reveals that only a portion of cerebellar Purkinje neurons are sensitive to ethanol enhancement of γ‐aminobutyric acid (GABA) responses. Although activation of beta‐adrenergic receptors permits ethanol enhancement of GABA function from some cerebellar Purkinje neurons, other neurons remain insensitive to ethanol. These findings are consistent with the finding that other external neural inputs are required to allow ethanol enhancement of GABA responses from Purkinje neurons. Because of a high expression of GABAB receptors on Purkinje cells, we tested whether activation of GABAB receptors might modulate the action of ethanol on GABA responsiveness.Methods: Extracellular single‐unit electrophysiological recording was used to investigate the effects of ethanol on responses to GABA and muscimol (a GABAA agonist) from cerebellar Purkinje neurons. Drugs tested were baclophen (a GABAB agonist) and CGP35348 (a GABAB antagonist).Results: Ethanol did not enhance responses to GABA and muscimol from all Purkinje neurons. Systemic administration of the GABAB agonist, baclophen (3 mg/kg intravenously), permitted ethanol to enhance GABA inhibition from ∼75% of cerebellar Purkinje neurons not initially enhanced by ethanol. Local iontophoretic application of baclophen to Purkinje neurons also allowed ethanol to enhance GABA and muscimol responsiveness from a portion of neurons in which ethanol initially did not affect their actions. An inhibitory action of ethanol on responses to GABA and muscimol, which was also influenced by baclophen, was observed from some Purkinje neurons. From Purkinje neurons initially sensitive to ethanol enhancement of GABA and muscimol function, administration of CGP35348, a GABAB antagonist, diminished the effect of ethanol on the responsiveness of these agonists from the majority (9/15) of neurons.Conclusions: The present findings demonstrated that baclophen allows ethanol enhancement of GABA and muscimol responsiveness from some, but not all, cerebellar Purkinje neurons initially not sensitive to ethanol. Likewise, a GABAB antagonist can diminish ethanol enhancement of GABA and muscimol responses from some ethanol‐sensitive neurons. Thus, these results emphasize that GABAB receptors on a portion of Purkinje neurons act as an auxiliary neural input that allows ethanol enhancement of GABA responses. Consequently, receptor structure alone does not account for the action of ethanol on GABAA receptor function on this cell type.
A Review of the Effects of Prenatal or Early Postnatal Ethanol Exposure on Brain Ligand‐Gated Ion Channels
Authors: Costa Edmar T. , Savage Daniel D. , Valenzuela C. Fernando 
Published: April 2006

Background: Ligand‐gated ion channels mediate fast excitatory and inhibitory synaptic transmission in the developing central nervous system. These channels have been shown to have roles in neuronal proliferation, differentiation, and programmed cell death. Numerous studies over the past 10 years indicate that prenatal and/or early postnatal ethanol exposure affects neurotransmitter‐gated ion channels.Methods: We conducted a review of the relevant literature, identified by a computer‐assisted literature search. This review presents an overview of studies performed with experimental preparations from the brains of rodents exposed to ethanol in utero and/or during the neonatal period and summarizes some of the salient issues that have developed in the course of these investigations. Differences in ethanol exposure paradigms and blood alcohol concentrations obtained in these studies are highlighted, and directions for future research are suggested.Results: Most studies have focused on the effects of prenatal or early postnatal ethanol exposure on NMDA receptors. These studies show that ethanol exposure affects ligand binding, subunit expression, and function of this receptor. Fewer studies have examined ethanol's effects on ligand‐gated ion channels other than NMDA receptors. For instance, a study reported changes in ligand binding to hippocampal kainate receptors. Another study found alterations in modulation of GABAA receptors by benzodiazepines and neurosteroids.Conclusions: These studies suggest that the effects of ethanol on brain ion channels may have a role in the pathophysiology of Alcohol‐Related Neurodevelopmental Disorders and Fetal Alcohol Syndrome.
Is There a Difference Between CAGE Interviews and Written CAGE Questionnaires?
Authors: Aertgeerts Bert , Buntinx Frank , Fevery Johan , Ansoms Stan 
Published: April 2006

Background: The CAGE questionnaire is a frequently studied and used instrument for screening of alcohol problems. It was developed and tested as a written questionnaire, but, clinically, it is often used as an oral interview. No comparisons have been made between the results of a written and an oral CAGE. This study attempted to (1) compare the results of a written CAGE questionnaire and a CAGE interview, and (2) compare the efficiency of using a simple open‐ended question about drinking habits before asking the CAGE and asking the CAGE without an introduction.Methods: All patients who attended a general internal medicine, cardiology, or hepatology clinic were classified according to the week of the consultation, as follows: group I (week 1), patients completed a written CAGE and were subsequently interviewed during a normal consultation by a physician, who also asked the CAGE questions; group II (week 2), a physician first interviewed the patients, including the CAGE, and subsequently patients completed a written CAGE; and group III (week 3), patients completed a CAGE interview after an open‐ended introduction (“What do you drink during the day?”). Kappa values were used to compare the answers of the written and oral CAGE interviews (groups II and I). Nonparametric ANOVA was used to compare the results of group III and the oral interview of group II.Results: Mean age was comparable between the groups, gender ratio was comparable between groups I and III, but there were fewer males in group II. Comparison of all written CAGEs with the oral CAGEs in the same patients resulted in an accuracy of 0.91 and a kappa value of 0.75 (95% CI, 0.66–0.84). No significant difference could be found between the results of the oral CAGE with or without an open‐ended introduction (p= 0.46).Conclusions: We found no difference between the oral and the written versions of the CAGE. This is important because most research results originate from written questionnaires. Our results do not support the finding that a different approach to the CAGE questions results in an increasing number of patients in which alcohol problems were detected.
The Expression of an Alcohol Deprivation Effect in the High–Alcohol‐Drinking Replicate Rat Lines Is Dependent On Repeated Deprivations
Authors: Rodd‐Henricks Zachary A. , McKinzie David L. , Murphy James M. , McBride William J. , Lumeng Lawrence , Li Ting‐Kai 
Published: April 2006

Background: The alcohol deprivation effect (ADE) is a temporary increase in the ratio of alcohol/total fluid intake and voluntary intake of ethanol (EtOH) solutions over baseline drinking conditions when EtOH access is reinstated after a period of alcohol deprivation. The ADE has been posited to be an animal model for alcohol craving. In the current study, we examined the effects of initial deprivation length and number of deprivation exposures on the ADE in the replicate lines of the high–alcohol‐drinking (HAD) rats.Methods: Adult male HAD‐1 and HAD‐2 rats received 24 hr free‐choice access to 10% (v/v) EtOH and water for 6 weeks. Rats were then assigned to groups deprived of EtOH for 0 (control), or 2 to 8 weeks. All deprived groups were then given 24 hr access to EtOH for 2 weeks before being deprived of EtOH for another 2 weeks. This cycle of 2 weeks of access and 2 weeks of deprivation was carried out for a total of four deprivations.Results: After the initial EtOH deprivation period, EtOH consumption in HAD‐1 and HAD‐2 rats returned to baseline levels but failed to exhibit either an early onset ADE (initial 2 hr) or prolonged ADE (24 hr). An ADE was observed in two of the four deprived groups for the HAD‐1 rats (2 week and 6 week groups) and in all deprived groups for the HAD‐2 rats after a second deprivation, and in all deprived groups of both lines after a third deprivation. In the HAD‐2 line, but not in the HAD‐1 line, the duration of the ADE was prolonged into the second reinstatement day after the fourth deprivation.Conclusions: The expression of an ADE was observed only after repeated deprivation periods in the HAD lines. The duration of the ADE was prolonged in the HAD‐2 line, but not in the HAD‐1 line, with repeated deprivations, which suggests a dissociation between selection for alcohol preference and the effects of repeated deprivations on the duration of the ADE.