bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain regional pharmacology of GABA A receptors in alcohol‐preferring AA and alcohol‐avoiding ANA rats
Authors: WONG GARRY , OVASKA TIMO , KORPI ESA 
Published: August 2003

AbstractCompounds interacting with the GABA A receptor system modulate voluntary alcohol consumption in alcohol‐preferring AA (Alko, Alcohol) rats. Therefore, we compared the central GABA A receptor pharmacology of the AA rats to that of their counterpart, alcohol‐avoiding ANA (Alko, Non‐Alcohol) rats with receptor autoradiography. Total flumazenil‐sensitive [3 H]Ro 15‐4513 binding to the benzodiazepine site of GABA A receptor was slightly lower in the hippocampus, striate cortex and lateral hypothalamus of the AA than ANA rats. The proportions of zolpidem‐ and diazepam‐sensitive components were similar in both rat lines. Basal picrotoxin‐sensitive [35 S]TBPS binding to the convulsant site of GABA A receptor was similar in most regions between the rat lines, but the up‐modulation of the binding by 10 μ M diazepam in the hippocampal, amygdaloid and entorhinal cortical areas was greater in the AA than ANA rats. These results do not reveal any general genetic defect in the GABA A receptors of AA or ANA rats, but the regional profile of the ligand binding differences between the lines, especially in the coupling of the benzodiazepine and chloride channel sites, suggests receptor subtype‐specific changes in brain regions implicated in behavioural reward and anxiolysis.
Performance in the cross‐maze and slip funnel tests of four pairs of rat lines selectively bred for divergent alcohol drinking behavior
Authors: SALIMOV R. M. , MCBRIDE W. J. , SINCLAIR J. D. , LUMENG L. , LI T.‐K. 
Published: August 2003

AbstractAlcohol naive rats from lines genetically selected for high and low alcohol drinking and founded on either Wistar (P/NP lines) and distinct heterogeneous stocks (AA/ANA and replicate HAD/LAD lines) were tested in the explorative cross‐maze and the inescapable slip funnel. Rats of the low alcohol‐consuming ANA, NP, LAD1 and LAD2 lines all exhibited a shorter latency before initiating exploration of the maze than did their high alcohol‐consuming counterparts (66, 51, 33 and 51% of the values for AA, P, HAD1 and HAD2 lines, respectively). Significant line differences were also found with the slip funnel test (AA > ANA for time in a sprawling posture; P > NP but HAD1 < LAD1 and HAD2 < LAD2 for time escaping), but the directions of line differences were not consistently related to those in alcohol drinking.
No association between D3 dopamine receptor (DRD3) alleles and cocaine dependence
Authors: FREIMER MARTIN , KRANZLER HENRY , SATEL SALLY , LACOBELLE JAMES , SKIPSEY KITZIA , CHARNEY DENNIS , GELERNTER JOEL 
Published: August 2003

AbstractCocaine is thought to act in the brain primarily by blocking dopamine re‐uptake. The dopamine D3 receptor (genetic locus DRD3) is localized to brain regions that have been implicated in the reinforcing effects of a number of substances of abuse, including cocaine. The DRD3 coding region contains a polymorphism identifiable as a polymerase chain reaction restriction fragment length polymorphism (PCR‐RFLP). This polymorphism leads to an amino acid substitution at position 9 in the extracellular N‐terminus of the D3 dopamine receptor. We examined alleles of the DRD3 gene in cocaine dependence using a genetic association strategy in samples of 62 white and 62 black cocaine‐dependent individuals. Comparisons were made with local (Connecticut) control subjects for both groups, and with a larger sample of literature controls (for the white subjects) and a contrast group of schizophrenic patients (for the black subjects). No association was found between cocaine dependence and DRD3 alleles in either group (Bonferroni corrected). There was a significant difference in allele frequency between whites and blacks. These results are consistent with no role for genetic variation of the D3 dopamine receptor in susceptibility to cocaine dependence.
Ethanol acutely impairs glycogen repletion in skeletal muscle following high intensity short duration exercise in the rat
Authors: PETERS TIMOTHY , NIKOLOVSKI SASHA , RAJA GHAZALA , PALMER T. NORMAN , FOURNIER PAUL 
Published: August 2003

AbstractEthanol is recognized to affect adversely carbohydrate metabolism in skeletal muscle. This paper seeks to establish whether ethanol acutely impairs glycogen repletion during recovery from high intensity short duration exercise in the rat. High intensity exercise caused the massive mobilization of glycogen stores in muscles rich in type IIa and IIb fibres and marked increases in plasma and muscle lactate levels. During the 30‐minute recovery period, there was substantial glycogen repletion in these muscles in both the ethanol‐treated and control rats. Ethanol, however, was associated with reduced glycogen resynthesis in both the tibialis anterior (by 22%) and red gastrocnemius (by 31%) muscles but not in the white gastrocnemius muscle. This reduction in post‐exercise glycogen deposition was accompanied by decreased lactate disposal and elevated plasma glucose levels. These effects of ethanol on glycogen repletion may involve interactions with hepatic gluconeogenesis, glucose uptake and utilization in muscle, muscle glycogen synthesis and lactate glyconeogenesis. The ethanol‐mediated impairment in post‐exercise glycogen repletion may have important implications for the pathogenesis of chronic alcoholic skeletal myopathy.
Cardiovascular risk factors in young drug addicts
Authors: BERG JOHN , HØSTMARK ARNE 
Published: August 2003

AbstractSince the type of life‐style often encountered in drug addicts is purported to influence their risk of cardiovascular disease, it seemed of interest to carry out a descriptive study on risk factors in young addicts. Twenty‐four young intravenous drug addicts, mean age 29 years and mean body mass index (BMI) 22.5 (kg/m−2), were compared with 24 healthy people matched for age, gender and BMI. Both groups responded to a questionnaire on life‐style risk factors. In addition, fasting blood samples were investigated for several coronary risk factors. Drug addicts had smoked more cigarettes (17 vs. 3 cigarettes/day) for a longer time period (15 vs. 5 years) than control subjects. They also had higher serum activities of liver enzymes related to alcohol abuse than controls. Level of physical activity and indicators of dietary intake of fruit, vegetables and salt were not significantly different between the groups. Blood lipid values, total cholesterol (5.1 vs. 5.6 mmol/l), and HDL‐cholesterol (1.2 mmol/l), apolipoproteins, and an atherogenic index reflecting the balance between the atherogenic low density lipoproteins (LDL) and the antiatherogenic fraction (HDL), as well as the smoking‐related factors fibrinogen and TBARS, were all similar in both groups. The study indicates that the prevalence of many known cardiovascular risk factors was similar in drug addicts and matched controls.
Interaction of mazindol with alcohol in mice
Authors: GEVAERD MONIQUE , TAKAHASHI REINALDO 
Published: August 2003

AbstractCombined anorectic‐alcohol misuse is a prevalent problem in Brazil. In order to understand better the interactive effects of ethanol (EtOH) and mazindol (MZ), we examined the effects of EtOH (1.2 g/kg) and MZ (5.0 mg/kg) given alone or in combination, on mouse behaviour. The results indicate that EtOH plus MZ induces a significantly greater increase in locomotor activity of mice than either constituent alone. However, no such interactive effect was detected in the place preference and in the plus‐maze test of anxiety. MZ given alone was found to increase the locomotor activity and to possess rewarding effects as measured in the place preference conditioning. At the dose selected, EtOH alone showed anxiolytic and rewarding effects. These results provide some evidence of increased behavioural effects in mice due to combinations of EtOH and MZ. These findings suggest that a major determinant of combined anorectic‐alcohol misuse may be the increased stimulating effects produced by such combination.
Book and Media Reviews
Authors: COOK CHRIS 
Published: August 2003

Books review in this article: Book reviews in this column will primarily be of titles focusing completely, or in part, on biological aspects of addiction. However, significant titles of general relevance to the addictions field will also be included, even if they are not “biological”, as will titles of general methodological and clinical relevance, even if they are not on “addictions”. Similar considerations will apply to other media (software, audio tapes and CDs, videos, etc). However, specific “addictions” software applications seem to be relatively uncommon and, as these items are rarely reviewed elsewhere, we will endeavour to include reviews of some of the older programmes that are still useful, as well as new titles that appear. I would appreciate suggestions of any items suitable for review, but especially software and other media of specific relevance to the addictions. Enzymology and Molecular Biology of Carbonyl Metabolism 5 H. WIENER, R. S. HOLMES & BENDICHT WERMUTH (Eds) Neurotransmitter Release and its Modulation: Biochemical Mechanisms, Physiological Function and Clinical Relevance D. A. POWIS & S. J. BUNN (Eds) Health Update No. 2—Smoking R. WALTERS & H. WENT Atlas of Clinical Gastroenterology, 2nd edn J. J. MISIEWICZ, A. FORBES, A. B. PRICE, P. J. SHORVON, D. R. TRIGER & G. N. J. TYTGAT Addiction Psychiatry: Current Diagnosis and Treatment N. S. MILLER Clinical Handbook of Psychotropic Drugs—5th revised edn KALYNA Z. BEZCHLIBNYK‐BUTLER & J. JOEL JEFFRIES Seminars in Psychiatric Genetics PETER MCGUFFIN, MICHAEL J. OWEN, MICHAEL C. O'DONOVAN, ANITA THAPAR & IRVING I. GOTTESMAN Genetic Analysis: Principles, Scope and Objectives J. R. S. FINCHAM PCR C. R. NEWTON (Ed.) Nucleic Acid Hybridization—Essential data P. M. GILMARTIN CRC Handbook of Chemistry and Physics, 76th edn D. R. LIDE (Ed.) The Biochemists' Songbook—2nd edn HAROLD BAUM SOFTWARE: SPSS for Windows v 6.1 EndNote Plus 2 and EndLink 2 for Windows BodyWorks version 4.0 on CD‐ROM Current Awareness in Biological Sciences
Alcoholism and the dopaminergic system: a review
Authors: NOBLE ERNEST 
Published: August 2003

AbstractAlcohol as well as other substances of abuse are reinforcing substances which manifest their effects through activation of the mesolimbic dopaminergic reward pathways of the brain. In animal genetic models of alcoholism, reduced dopamine levels and D2 dopamine receptor (DRD2) numbers have been found in the brains of alcohol‐preferring animals. Dopamine receptor agonists reduce alcohol consumption, whereas antagonists, in general, show the opposite effect. Moreover, quantitative trait loci studies in animals suggest the DRD2 gene and the region proximate to this locus is a chromosomal “hot spot” for alcohol‐related behaviors. Human studies provide additional support for connection between alcohol dependence and CNS dopaminergic function. In endocrinological studies, using dopamine receptor agonists, reduced dopaminergic activity has been found in more severe and more genetic types of alcoholics. Brain imaging studies are similarly revealing a diminished dopaminergic tone in alcoholics. Treatment of alcoholics with dopamine receptor agonists shows reduced alcohol consumption and improvements in other outcome measures. Molecular genetic studies in humans have identified an association of the Al allele of the DRD2 gene with alcoholism. Moreover, a diminished central dopaminergic function has been found in DRD2 A1 allele subjects using pharmacological, electrophysiological and neuropsychological studies. Further, treatment of alcoholics with a dopamine receptor agonist showed more salutary effects on alcoholics who carry than those who do not carry the DRD2 A1 allele. The A1 allele has also been associated with substance use disorders other than alcoholism, including and cocaine and nicotine dependence and polysubstance abuse. The emerging evidence suggests that the DRD2 is a reinforcement or reward gene. It could represent one of the most prominent single‐gene determinants of susceptibility to severe substance abuse. However, the environment and other genes, when combined, still play the larger role.
Alcohol dehydrogenases and aldehyde dehydrogenases among inbred strains of mice: multiplicity, development, genetic studies and metabolic roles
Authors: ROUT UJJWAL , HOLMES ROGER 
Published: August 2003

AbstractAlcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the major enzymes responsible for the metabolism of alcohols and aldehydes in the body. Both exist as a family of isozymes in mammals, and have been extensively studied in animal models, particularly among inbred strains of mice. Mouse ADH exists as at least three major classes, which are predominantly localized in liver (classes I and III), and in stomach/cornea (class IV). Mouse ALDH exhibits extensive multiplicity, several forms of which have been characterized, including ALDH1 (liver cytoplasmic/class 1 isozyme); ALDH2 (liver mitochondrial/class 2.); ALDH3 (stomach cytosolic/class 3); ALDH4 (liver microsomal/class 3); and ALDH5 (testis cytosolic/class 3). Biochemical, genetic and molecular genetic analyses have been performed on several of these enzymes, including studies on variant forms of ADH and ALDH. Distinct metabolic roles are proposed, based upon their tissue and subcellular distribution characteristics and the biochemical properties for these enzymes.
Pathogenesis of alcoholic hepatic steatosis
Authors: SIMPSON K. J. 
Published: August 2003

AbstractChronic alcohol misuse is the most common cause of hepatic steatosis. The accumulation of lipid is reversible with abstinence, but some workers have suggested that the severity of hepatic steatosis predicts the progression with time to alcoholic cirrhosis. Triacylglycerol is the major accumulating lipid and subcellular fractionation and electron microscopy studies have shown accumulation of lipid droplets within the golgi fraction. This is consistent with the reports in both experimental animals and man of reduced hepatic secretion of very low density lipoprotein triacylglycerol which may be secondary to acetaldehyde‐induced disruption of the cytoskeletal elements. In addition, hepatic production of triacylglycerol increases, but most studies in animal models suggest that increased triacylglycerol synthesis becomes less important as hepatic lipid accumulates.
The effects of acute administration of ethanol on jejunal protein synthesis and circulating insulin‐like growth factor (IGF)‐1 and IGF binding proteins in ad libitum fed and nutritionally restricted rats
Authors: MIELL JOHN , MARWAY JASPAUL , JONES JENNY , PREEDY VICTOR 
Published: August 2003

AbstractThe effects of acute ethanol administration (75 mmol/kg body weight) to male Wistar rats (either ad libitum fed or nutritionally restricted) on fractional rates of protein synthesis in the jejunum was assessed together with the changes in IGF‐1 and IGF binding protein concentrations. Acute administration of ethanol resulted in significant decreases in fractional rates of protein synthesis in the whole jejunum and jejunal seromuscular layers of both the ad libitum fed and nutritionally restricted animals. The synthesis rate per unit RNA (k RNA, mg protein/day/mg RNA) in whole jejunum was reduced by 29% and 24% in the nutritionally restricted and ad libitum fed animals, respectively. Mean IGF‐1 levels were lower in the nutritionally restricted group (871 ± 36.9 μ g/l) than the ad libitum animals (960 ± 27.3 μ g/l) although this did not reach significance. In contrast, administration of alcohol to both groups markedly reduced circulating IGF‐1 levels (ad libitum : 518 ± 19.8 μ g/l, nutritionally restricted: 417 ± 33.7 μ g/l). Furthermore, ethanol treatment resulted in a three‐fold increase in the intensity of a 30 kDa IGF binding protein (IGFBP) in the ad libitum fed animals and a fourfold increase in both 30 and 32 kDa IGFBP bands in the nutritionally restricted group as visualized by Western ligand blotting. Decreases in levels of IGF‐1 allied with increased circulating small molecular weight IGFBPs may contribute to the reduction in fractional rates of protein synthesis in the gastrointestinal tract of ethanol‐treated rats.
Acetaldehyde metabolism by liver mitochondrial ALDH from UChA and UChB rats: effect of inhibitors
Authors: TAMPIER LUTSKE , SÁNCHEZ ELIANA , ELENA MARÍA 
Published: August 2003

AbstractWe have observed that blood acetaldehyde (AcH) levels after an ethanol dose were significantly higher in disulfiram‐pre‐treated UChA (low ethanol consumer) than in UChB (high ethanol consumer) rats. In order to explore these results further, we studied the effect of disulfiram (300 mg/kg i.p.) and chlorpropamide (80) mg/kg i.p.) pre‐treatment on blood AcH levels after oral ethanol (60 mmol/kg) and on AcH metabolism by liver mitochondrial aldehyde(s) dehydrogenase(s) from UChA and UChB rats. AcH metabolism by liver mitochondrial aldehyde dehydrogenase (ALDH) was studied by following AcH disappearance rate and the formation of NADH at 340 nm in the incubation medium. The results showed that chlorpropamide, like disulfiram, produced a higher blood AcH level consistent with a greater inhibition of the low‐Km mitochondrial ALDH in the UChA rats than in the UChB rats. These drugs did not inhibit the high Km mitochondrial ALDH. Kinetic studies of mitochondrial ALDH show that low‐Km mitochondrial ALDH from UChB rats exhibits a higher affinity for NAD than UChA rats. This observation could explain the different inhibition of ALDH by both drugs, assuming that the inhibitors reduce NAD availability, the rate limiting step in the mitochondrial ALDH oxidation.
Salivary glands in alcoholism: a histologic and sialographic study
Authors: SMITH PATRICIO , RAMIREZ JULIO , ROMO RAFAEL , ESGUEP ALFREDO 
Published: August 2003

AbstractA qualitative and quantitative histological analysis of minor salivary glands was carried out in 60 alcoholics (20 alcoholics with liver damage, 20 without liver damage, 20 young alcoholics) and 20 matched control patients. A sialographic study was carried out in the same 60 alcoholic patients and in 40 non‐alcoholic control individuals. Minor salivary gland biopsies were obtained and samples were processed for light microscopy. A quantitative morphometrical assessment was carried out by counting the number of acinar cells with a squared grid eye‐piece. Both experimental and control samples presented very similar results demonstrating that, at least in this study, minor salivary glands do not develop hypertrophic, atrophic or hyperplastic changes. We detected a statistical difference between adult alcoholics without liver damage and adult alcoholics with liver damage. A diffuse mononuclear inflammatory cell infiltrate was distributed through the stroma or concentrated around the salivary ducts in both experimental and control samples. Acinar degeneration and hyperaemia were common changes observed in both experimental and control samples. Sialographic images from alcoholics demonstrated a similar morphology when compared with control patients, perhaps a reduction in secondary ducts diameter was observed in alcoholic patients. From this study we may conclude that minor salivary glands are scarcely affected by alcoholism, even when this disease has progressed to liver damage. Based on a presentation to the Latin‐American Society for Biomedical Research on Alcoholism (LASBRA), November 1994 at Santiago, Chile
Influence of age and of pre‐treatment with D‐cycloserine on the behavior of ethanol‐treated rats tested in the elevated plus‐maze apparatus
Authors: FERREIRA VÂNIA MARIA MORAES , MORATO GINA STRUFFALDI 
Published: August 2003

AbstractThere is evidence that ethanol is able to influence central functions through the antagonism of the NMDA‐receptor system. It has been shown that this system is also involved in the modulation of anxiety‐related behavior in rats. Recently, we observed gender‐ and age‐related behavioral influences in rats tested on the elevated plus‐maze apparatus The present study was undertaken in order to investigate: (1) the effects of ethanol (0.8, 1.0 or 1.2 g/kg, i.p.) on the behavior of male and female rats tested on the elevated plus‐maze at 2, 3, 4 or 5 months of age; (2) the effect of the pre‐treatment with D‐cycloserine (3.0 or 6.0 mg/kg), an agonist of the glutamate NMDA‐receptor system, 30 min before the ethanol (1.2 g/kg) injections, in rats tested in the elevated plus‐maze at 2 months or 4 months of age. The results demonstrated that ethanol did not affect the time spent and the frequency of entries on the open arms of the elevated plus‐maze in rats tested at 2 months of age, but increased these parameters in older animals. Moreover, the results showed that D‐cycloserine, at doses that did not affect the behavior of control animals, antagonized the increased frequency of entries and time spent on open arms produced by ethanol in rats tested at 4 months of age. Our results suggest an age‐related influence on the anxiolytic action of ethanol in rats tested in the elevated plus‐maze. Moreover, the results suggest that the NMDA‐receptor system can be involved in this effect, and strengthens the evidence for the participation of the NMDA‐receptor system in anxiety‐related behavior.
Role of parasympathetic (vagal) cardiac control in elevated heart rates of smokers
Authors: HIRSCH JUDITH ANN , BISHOP BEVERLY , YORK JAMES 
Published: August 2003

AbstractSmokers may develop chronic increases in cardiac rate and alterations in cardiovascular control. If the increased mean heart rate (HR) in cigarette smokers is due in part to a deficit in vagal cardiac rate control, this should be reflected in a decreased amplitude of respiratory sinus arrhythmia (RSA). To test this hypothesis we studied 36 smokers and 36 non‐smokers, matched for age, race, gender and blood pressure. All subjects were studied in the supine and seated positions. Mean heart rate was determined from the ECG during 30 s of quiet breathing; RSA was determined for 10 consecutive deep (>50% vital capacity) slow (5‐7/min) breaths. Mean HRs in smokers were significantly higher than in non‐smokers, but the increases in mean HRs evoked by a shift from the supine to seated position were lower in smokers than in non‐smokers, suggesting that chronic tobacco use may alter the relative contributions of sympathetic and parasympathetic control of cardiac rate. Because neither the RSAs nor the position‐dependent increase in RSA were different between smokers and non‐smokers, we conclude that the elevated mean HRs in smokers were not the result of decreased respiratory or vasomotor modulation of vagal cardiac control, but instead were the result primarily of sympathetic stimulation.
Acute ethanol‐mediated insulin resistance in the rat: the role of ethanol oxidation
Authors: DHILLON AMARDEEP , XU DAN , PALMER T. NORMAN 
Published: August 2003

AbstractEthanol causes an acute and profound insulin resistance in humans and in the rat. Recent studies indicate that defects in skeletal muscle glucose uptake and utilization make a major contribution to this insulin resistance. In this study, we used the euglycaemic hyperinsulinaemic clamp to examine the role that hepatic ethanol oxidation via alcohol dehydrogenase (ADH) plays in the acute insulin resistance caused by ethanol in the rat. Treatment with the ADH inhibitor 4‐methylpyrazole (4‐MP) failed to abolish the insulin resistance as expressed as a decrease in the rate of glucose infusion required to maintain euglycaemia (GIR). A decrease in GIR was also observed in response to tert‐butanol, an alcohol that is not a substrate for hepatic ADH. These results indicate that oxidation via ADH is not a prerequisite for the inhibition by ethanol of whole‐body glucose utilization. In a separate study, we examined the relationship between blood ethanol concentration and GIR in order to determine the potency of ethanol in causing insulin resistance. These experiments showed that even at low blood concentrations (<2 mM), ethanol caused a profound decrease in GIR, similar in magnitude to that observed at higher blood concentrations (approximately 40 mM)