bluuebunny/crossref_metadata_2025_split huggingface dataset:
Permanent Neuronal Cell Loss in the Inferior Olive of Adult Rats Exposed to Alcohol during the Brain Growth Spurt: A Stereological Investigation
Authors: Napper Ruth M. A. , West James R. 
Published: April 2006

The purpose of this study was to examine whether exposure of rat pups to alcohol postnatally over a period of brain development similar to that of the human 3rd trimester results in a permanent loss of cells in the inferior olivary nucleus. It was hypothesized that a deficit of neurons in the inferior olive, the sole source of climbing fibers, may contribute to the cerebellar dysfunction observed following exposure to alcohol during development.Sprague‐Dawley rat pups were artificially reared and administered alcohol over postnatal days 4–9. One artificially reared group received a daily alcohol dose of 4.5 g/kg, administered as a 10.2% solution in 2 of 12 daily feedings (10.2% group). This pattern of alcohol administration resulted in high peak blood alcohol concentrations with near total clearance. The other artificially reared group was fed a diet made isocaloric to the alcohol‐containing diet (gastrostomy control group). Pups were allowed to grow to adulthood and killed on postnatal day 115. The total number of neurons in the inferior olivary nucleus was estimated using unbiased stereological methods.Exposure to alcohol resulted in a significant deficit in the number of neurons in the inferior olive at 115 days of age. The total number of neurons in the alcohol‐exposed group was 40.12 ± 8.7 ± 103, compared with 53.37 ± 3.7 ± 103 in the artificially reared controls.These results indicate that there is a permanent deficit of neurons in the inferior olive after postnatal exposure to alcohol. This supports the hypothesis that cerebellar dysfunction after exposure to alcohol during the brain growth spurt may be the result of more extensive neuronal deficits than previously thought.
Effects of Chronic Alcohol Consumption and Aging on Dopamine D1 Receptors in Fischer 344 Rats
Authors: Woods James M. , Ricken John D. , Druse Mary J. 
Published: April 2006

The present study examined the hypothesis that chronic alcoholism augments the age‐related loss of dopamine D1 receptors. This hypothesis was investigated because previous studies reported that both aging and chronic alcoholism produce significant changes in dopaminergic systems, and because chronic alcoholism potentiates some age‐related CNS losses. In addition, this study investigated the effects of aging on D1 receptors in animals 1 and 7 days after withdrawal from chronic ethanol. Quantitative autoradiography was used to measure [3H]SCH 23390 binding to D1 receptors in brain areas associated with both the nigrostriatal and mesocorticolimbic dopamine systems. Receptors were assessed in 5‐, 14‐, and 24‐month‐old male Fischer 344 rats that were pair‐fed a control or 6.6% (v/v) ethanol‐containing liquid diet for 6 weeks.The results of these studies demonstrated that aging is associated with a significant decline in D1 receptors in the rostral and caudal striatum, and substantia nigra of both control and ethanol‐fed rats. These receptor changes in the nigrostriatal system may be associated with motor abnormalities. In addition, there was an age‐related decline in D1 receptors in two brain areas of the mesocorticolimbic system: the nucleus accumbens and frontal cortex. The latter findings may be important because of the involvement of this system with the rewarding properties of ethanol and other drugs of abuse. There were no age‐related differences in the response of D1 receptors to ethanol withdrawal in the caudal and rostral striatum, substantia nigra, and nucleus accumbens. Consumption of the 6.6% (v/v) ethanol‐containing liquid diet for 6 weeks did not augment any of the age‐related losses of D, receptors. Nonetheless, we cannot eliminate the possibility that either a more prolonged ethanol exposure or consumption of a higher dose of ethanol would have had more pronounced effects on the young to aged rats.
No Sex and Age Influence on the Expression Pattern and Activities of Human Gastric Alcohol and Aldehyde Dehydrogenases
Authors: Lai Ching‐Long , Chao You‐Chen , Chen Yi‐Chyan , Liao Chin‐Shya , Chen Mei‐Chun , Liu Yee‐Chun , Yin Shih‐Jiun 
Published: April 2006

Background: Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the principal enzymes responsible for ethanol metabolism in humans. The stomach is involved in the metabolism of alcohol during absorption. Conflicting reports exist with regard to the influence of sex and age on the activity of ADH in the human gastric mucosa. The purpose of the present study was to determine the effects of age and sex on the expression pattern and activities of stomach ADH and ALDH.Methods: A total of 115 endoscopic gastric biopsy specimens were investigated from Han Chinese men (n= 70) and women (n= 45) aged 20–79 years with approximately even distribution among 10‐year age intervals. The expression patterns of ADH and ALDH were identified by isoelectric focusing, and the activities were assayed spectrophotometrically.Results: The expression patterns of gastric ADH and ALDH remained unchanged with respect to sex and age. At 33 mM or 500 mM ethanol, pH 7.5, the ADH activities did not differ significantly among the various age groups or between men and women. At 200 μM or 20 mM acetaldehyde, the ALDH activities did not differ significantly in relation to sex and age. No correlations were found between the ADH or ALDH activities at both the high and low substrate concentrations and the ages in men and women.Conclusions: The results indicate that there is no significant effect of either sex or age on the expression pattern and activity of ADH and ALDH in the human gastric mucosa. The stomach ADH seems unlikely to account for possible variations in the first‐pass metabolism of alcohol with regard to sex and age.
Effects of Alcohol on the Response to Hyperventilation of Participants High and Low in Anxiety Sensitivity
Authors: MacDonald Alan B. , Baker Jan M. , Stewart Sherry H. , Skinner Michelle 
Published: April 2006

Background: Previous research suggests that high levels of anxiety sensitivity (AS; fear of anxiety symptoms) may constitute a risk factor for alcohol abuse. The present study evaluated the hypothesis that high AS levels may increase risk for alcohol abuse by promoting a heightened sober reactivity to theoretically relevant stressors and heightened sensitivity to alcohol's emotional reactivity dampening effects, which would negatively reinforce drinking in this population.Methods: One hundred and two undergraduate participants (51 high AS, 51 low AS) with no history of panic disorder were assigned to either a placebo, low‐dose alcohol, or high‐dose alcohol beverage condition (17 high AS, 17 low AS per beverage condition). After beverage consumption and absorption, participants underwent a 3 min voluntary hyperventilation challenge.Results and Conclusions: High‐AS/placebo participants displayed greater affective and cognitive reactivity to the challenge than low‐AS/placebo participants, which indicated increased fear and negative thoughts (e.g., “losing control”) during hyperventilation among sober high AS individuals. Dose‐dependent alcohol dampening of affective and cognitive reactivity to hyperventilation was observed only among high‐AS participants, which suggested that high‐AS individuals may be particularly sensitive to alcohol‐induced reductions in their degree of fear and negative thinking in response to the experience of physical arousal sensations. In contrast, dose‐dependent alcohol dampening of self‐reported somatic reactivity was observed among both high‐ and low‐AS participants. We discuss implications of these results for understanding risk for alcohol abuse in high‐AS individuals, as well as directions for future research.
Effects of Moderate and High Doses of Alcohol on Attention, Impulsivity, Discriminability, and Response Bias in Immediate and Delayed Memory Task Performance
Authors: Dougherty Donald M. , Marsh Dawn M. , Moeller F. Gerard , Chokshi Reena V. , Rosen Valerie C. 
Published: April 2006

Background: Prior studies that examined the effects of alcohol on Continuous Performance Test (CPT) performance have resulted in inconsistent outcomes. Most studies that examined the effects of alcohol on concentrated attention tasks (like the CPT) found little effect of alcohol on performance measures, even when doses that exceeded 0.8 g/kg were used. One likely reason for these inconsistencies is the varying difficulty (and sensitivity) of the task used, and as a result, comparisons between studies are difficult. This study is one in a series that examines the effects of alcohol on attention by using a difficult version of the CPT (Immediate and Delayed Memory Task—IMT/DMT). Our purpose for these studies has been two‐fold, examining the effects of alcohol (1) on concentrated attention (i.e., correct detections) and (2) on errors (i.e., commission errors) previously correlated with impulsive behaviors. The first is important because previous studies have shown little effect of alcohol on attention, and the second is important because commission errors have been related to impulsive behaviors.Methods: In the IMT/DMT, participants respond to a briefly displayed number when it is identical to the one displayed before it. The procedure includes immediate and delayed conditions where successive stimuli to be matched are delayed by 0.5 sec or by 3.5 sec. The three stimulus types included target (identical match), catch (four of five digits match), and filler (no match) stimuli. Twenty subjects completed this task after consuming either a placebo drink or a drink that contained 0.5 g/kg or 1.0 g/kg of alcohol on different days.Results: The main findings were that (1) alcohol decreased the percentage of correct identifications of target stimuli; (2) alcohol increased the percentage of commission errors in relation to the number of correct target responses; and (3) alcohol decreased discriminability whereas response bias became more conservative.Conclusions: These results clearly demonstrated a time‐course effect of the 1.0 g/kg alcohol dose on attention, impulsivity, discrimination, and response criteria when a variety of dependent measures are used.
Binge Ethanol Consumption Causes Differential Brain Damage in Young Adolescent Rats Compared With Adult Rats
Authors: Crews Fulton T. , Braun Christopher J. , Hoplight Blair , Switzer Robert C. , Knapp Darin J. 
Published: April 2006

Background:Adolescents respond differently to alcohol than adults. Furthermore, binge drinking in young adolescents is becoming increasingly common.Methods:To determine if the effects of binge drinking on brain damage are different in juveniles compared with adults, the effects of a 4 day binge ethanol treatment (e.g., 4 days of 4 times per day 15% ethanol intragastrically, approximately 9–10 g/kg/day ethanol) were investigated in adolescent‐juvenile rats (JVN) 35 days old and compared with adult (ADT) rats 80 to 90 days old. Brain damage was measured by using the amino cupric silver stain of de Olmos et al. (1994).Results:Significant brain damage was found in both groups. The olfactory bulbs were equally damaged in both groups; however, the associated frontal cortical olfactory regions were damaged only in JVN. The anterior portions of the piriform and perirhinal cortices also were damaged only in JVN rats. Quantitation of silver‐stained frontal areas in binge ethanol‐treated JVN rats ranged from 400% to 1260% of control values. For example, in anterior perirhinal cortex, silver stain increased from 48 ± 14 to 444 ± 114 (mm2× 103argyrophilic area;p< 0.01) in JVN control and binge ethanol‐treated animals, respectively. In contrast, posterior perirhinal cortex showed greater damage in adults, being 236 ± 76 vs. 875 ± 135 (mm2× 103argyrophilic area;p< 0.005) in JVN and ADT, respectively.Conclusions:The young‐adolescent brain shows differential sensitivity to alcohol‐induced brain damage compared with adults.
Serotonergic Modulation of Ethanol‐Induced Electrophysiological Depression in Young and Aged Rats
Authors: Jeng Churn‐Hueih , Chou Jenny R. , Hoffer Barry J. , Wang Yun 
Published: April 2006

Background: Ethanol (EtOH)‐induced electrophysiological depressions in cerebellar Purkinje neurons have been shown to be potentiated by exogenously applied serotonin (5HT). In this study, we determined whether this modulatory action can be activated by endogenous release from presynaptic serotonergic terminals, and whether such a response is altered by age or rat strain.Methods: Extracellular 5HT levels in cerebellar cortex were measured in real time by in vivo chronoamperometry, by using Nafion‐coated carbon fiber electrodes, in anesthetized young (3–5 months old) or aged (18–24 months old) Sprague Dawley and Fischer 344 rats. Some animals were prelesioned with 5,7 dihydroxytryptamine (5,7 DHT). Single unit electrophysiological activity was recorded from cerebellar Purkinje neurons. Serotonin or its presynaptic antagonist methiothepin was applied directly to cerebellar neurons through multibarrel pipettes.Results: Local application of methiothepin dose‐dependently induced 5HT overflow in young Sprague Dawley and Fisher 344 rats. Methiothepin‐induced 5HT release was decreased significantly in aged or 5,7 DHT‐lesioned rats. Local application of methiothepin or 5HT potentiated EtOH‐induced electrophysiological depression of Purkinje neurons in young animals of both strains. Methiothepin‐potentiated, EtOH‐elicited neuronal inhibition was reduced greatly in aged or 5,7 DHT‐lesioned rats. Serotonin‐facilitated EtOH responses were reduced in the aged Sprague Dawley rats.Conclusions: EtOH‐induced electrophysiological responses in cerebellum can be facilitated by endogenous 5HT release by using a 5HT autoreceptor antagonist. Such actions are attenuated in aged rats perhaps through a presynaptic serotonergic mechanism.
A Characterization of Approach and Avoidance Learning in High–Alcohol‐Drinking (HAD) and Low–Alcohol‐Drinking (LAD) Rats
Authors: Blankenship Matthew R. , Finn Peter R. , Steinmetz Joseph E. 
Published: April 2006

Background: This study was undertaken as one of a series of experiments designed to examine basic behavioral characteristics present in rats bred specifically for alcohol preference. The basic premise for these experiments has been the idea that alcohol‐preferring and ‐nonpreferring rats may differ in basic activation and inhibition control mechanisms that govern behavior and that different lines of alcohol‐preferring rats may demonstrate differential deficits in behavioral activation and behavioral inhibition tendencies. In the present experiment, conditioned approach and avoidance behaviors were studied in alcohol‐naïve high–alcohol‐drinking (HAD), low–alcohol‐drinking (LAD), and N/NIH rats to evaluate behavioral activation in this line of rats.Methods: High alcohol drinking (HAD1), low alcohol drinking (LAD1), and N/Nih stock rats were trained to press a response bar during a tone signal to avoid a mild foot shock or receive a food reward. In addition, HAD2 and LAD2 rats, independently‐bred replicate lines of the HAD1/LAD1 rats, were trained on the avoidance task.Results: Although the HAD1 rats easily learned the appetitive version of the bar‐pressing task, they did not learn the avoidance response. The LAD1 and N/Nih rats learned both the approach and the avoidance tasks normally. Similar to HAD1 rats, the HAD2 rats did not learn the avoidance response whereas LAD2 rats showed significant avoidance performance levels.Conclusions: The present data demonstrated that both HAD1 and HAD2 rats had a rather specific behavioral activation deficit: although they easily learned to press a bar to receive food reinforcement, they did not learn to press the bar to avoid a foot shock. We speculate that this failure to learn the avoidance response may be related to heightened anxiety in the HAD rats and that this excessive anxiety may lead to the development of high levels of alcohol consumption in these selectively bred rats.
Reliability and Concurrent Validity of DSM‐IV Subclinical Symptom Ratings for Alcohol Use Disorders Among Adolescents
Authors: Bailey Susan L. , Martin Christopher S. , Lynch Kevin G. , Pollock Nancy K. 
Published: April 2006

Background: The concurrent validity of subclinical ratings for psychiatric symptoms can help refine symptom definitions and threshold criteria. However, virtually no research has examined subclinical ratings for DSM‐IV symptoms in psychiatric diagnostic interviews. This study examined the frequency, reliability, and concurrent validity of subclinical ratings for 11 symptoms of alcohol use disorders among adolescents.Methods: Subjects were 239 male and 164 female adolescents ages 14 to 18 recruited from treatment and community sources. Symptoms and diagnoses were made with an adapted version of the Structured Clinical Interview for the DSM‐IV.Results: Subclinical ratings showed acceptable to high interrater reliability. The proportion of subclinical ratings tended to decrease with increasing levels of alcohol problems. For 10 of the 11 symptoms, subjects with subclinical ratings were distinguished from those with absent and/or those with present ratings. Subjects with subclinical ratings were often distinct from those with present ratings but less often distinct from those with absent ratings.Conclusions: For most of the DSM‐IV alcohol use disorder symptoms, subclinical ratings appear to be reliable and valid and provide information beyond dichotomous symptom classifications for adolescents. Threshold criteria appear to be appropriate in many cases, but boundaries between absent and subclinical ratings are “fuzzy.” Practical and research implications are discussed.
Heavy Drinking, Alcohol Dependence, and Injuries at Work Among Young Workers in the United States Labor Force
Authors: Veazie Mark A. , Smith Gordon S. 
Published: April 2006

Background: To determine whether heavily drinking and alcohol‐dependent workers are at higher risk of occupational injury, we analyzed the nationally representative cohort of people enrolled in the National Longitudinal Survey of Youth since 1979.Methods: This analysis was restricted to the 8569 respondents in the 1989 annual interview (age 24–32) who were employed during the 6 months before the interview. We studied occupational injuries (excluding sprains or strains) reported within 6 months of the interview in 1989 (cross‐sectional analysis) and 1990 (prospective analysis).Results: Among current drinkers, significant two‐fold increases in the odds of injury for one or more episodes of heavy drinking were reduced to an odds ratio (OR) of 1.2 (95% confidence interval [CI] = 0.7, 2.1) in the cross‐sectional analysis and an OR of 1.6 (CI 1.0, 2.8) in the prospective analysis after adjustment for confounding. No dose‐response relationship with the frequency of heavy drinking was found. Alcohol‐dependent respondents were not at higher risk of injury in the cross‐sectional (OR = 1.1, CI 0.7, 1.8) or prospective (OR = 1.3, CI 0.8, 2.2) analyses after adjustment for confounding.Conclusions: For young U.S. workers, common occupational injuries (excluding sprains and strains) may not be strongly associated with alcohol dependence. Confounding by other risk factors may explain much of the association between being a heavy drinker and occupational injuries in this population.
Increased Distractibility by Task‐Irrelevant Sound Changes in Abstinent Alcoholics
Authors: Ahveninen Jyrki , Jääskeläinen Iiro P. , Pekkonen Eero , Hallberg Anja , Hietanen Marja , Näätänen Risto , Schröger Erich , Sillanaukee Pekka 
Published: April 2006

Background: Chronic alcoholism is accompanied by “frontal” neuropsychological deficits that include an inability to maintain focus of attention. This might be associated with pronounced involuntary attention shifting to task‐irrelevant stimulus changes and, thereafter, an impaired reorienting to the relevant task. The neural abnormalities that underlie such deficits in alcoholics were explored with event‐related potential (ERP) components that disclosed different phases of detection and orienting to stimulus changes.Methods: Twenty consecutive abstinent male alcoholics (DSM‐IV) and 20 age‐matched male controls (healthy social drinkers) were instructed to discriminate equiprobable 100 and 200 msec tones in a reaction‐time task (RT) and to ignore occasional, either slight (7%) or wide (70%), frequency changes (hypothesized to increase RT) during an ERP measurement.Results: In the alcoholics, we found pronounced distractibility, evidenced by a RT lag (p < 0.01) caused by deviants, that correlated (Spearman ρ= 0.5) with a significantly enhanced (p < 0.01) amplitude of mismatch negativity (MMN) to deviants. Significantly increased RT lag for trials subsequent to deviants (slight p < 0.001, wide p < 0.05) in the alcoholics suggested impaired reorienting to the relevant task. The MMN enhancement also predicted poorer hit rates in the alcoholics (Spearman ρ= 0.6–0.7). Both the MMN enhancement and pronounced distractibility correlated (Spearman ρ= 0.4) with an early onset of alcoholism.Conclusions: Attentional deficits in the abstinent alcoholics were indicated by the increased distractibility by irrelevant sound changes. The MMN enhancement suggested that this reflects impaired neural inhibition of involuntary attention shifting, being most pronounced in early‐onset alcoholics.
Ethanol Inhibits Insulin Receptor Tyrosine Kinase
Authors: Seiler Andrea E. M. , Henderson Aaron , Rubin Raphael 
Published: April 2006

Background: Ethanol inhibits insulin‐like growth factor‐I (IGF‐I) and insulin signaling in various cell types. The tyrosine autophosphorylation of the IGF‐I and insulin receptors appears to be a target for ethanol, as well as other receptor tyrosine kinases.Methods and Results: The effect of ethanol on purified recombinant insulin receptor kinase activity was examined. A noncompetitive inhibition was observed at pharmacologically relevant concentrations of ethanol. Both peptide substrate tyrosine phosphorylation and kinase autophosphorylation are inhibited by ethanol. Near equivalent inhibition of kinase activity was noted for 300 mM methanol, 150 mM ethanol, 20 mM 1‐propanol, and 10 mM 1‐butanol.Conclusion: The findings identify a direct protein interaction site of ethanol, and provide insight into the mechanism by which ethanol inhibits receptor tyrosine kinase activity.
Gene Expression in Human Alcoholism: Microarray Analysis of Frontal Cortex
Authors: Lewohl Joanne M. , Wang Long , Miles Michael F. , Zhang Li , Dodd Peter R. , Harris R. Adron 
Published: April 2006

Background: Changes in brain gene expression are thought to be responsible for the tolerance, dependence, and neurotoxicity produced by chronic alcohol abuse, but there has been no large scale study of gene expression in human alcoholism.Methods: RNA was extracted from postmortem samples of superior frontal cortex of alcoholics and nonalcoholics. Relative levels of RNA were determined by array techniques. We used both cDNA and oligonucleotide microarrays to provide coverage of a large number of genes and to allow cross‐validation for those genes represented on both types of arrays.Results: Expression levels were determined for over 4000 genes and 163 of these were found to differ by 40% or more between alcoholics and nonalcoholics. Analysis of these changes revealed a selective reprogramming of gene expression in this brain region, particularly for myelin‐related genes which were down‐regulated in the alcoholic samples. In addition, cell cycle genes and several neuronal genes were changed in expression.Conclusions: These gene expression changes suggest a mechanism for the loss of cerebral white matter in alcoholics as well as alterations that may lead to the neurotoxic actions of ethanol.