bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Alcohol Use Disorders Identification Test (AUDIT) and Carbohydrate‐Deficient Transferrin (CDT) in a Routine Workplace Health Examination
Authors: Hermansson Ulric , Helander Anders , Huss Anders , Brandt Lena , Rönnberg Sten 
Published: May 2006

Background:Only a few studies on workplaces have examined the Alcohol Use Disorders Identification Test (AUDIT) or carbohydrate‐deficient transferrin (CDT) as screening instruments for the early identification of elevated and risky levels of alcohol consumption. The purpose of this study was to compare the performances of AUDIT, CDT, and γ‐glutamyltransferase (GGT) in a routine health examination (alcohol screening) in the workplace.Methods:The study, carried out over 16 months in a large workplace in the transport sector, was part of an on‐going controlled study. Employees who came to the company health service for a routine health examination were offered the opportunity to undergo an alcohol screening and check their alcohol habits.Results:Of the 570 subjects who participated, 105 (18.4%) screened positive according to AUDIT, CDT, or both. Only 7.6% of the persons who screened positive did so according to both instruments. If GGT had been included as a screening instrument, the proportion of positive results would have increased to 22.0%. If we had only used AUDIT in the screening process, the proportion of positives would have fallen by nearly half.Conclusions:The present findings suggest that AUDIT and CDT are complementary instruments for alcohol screening in a routine workplace health examination, and each has value for identifying a different segment of the risky drinking population.
Association Between Ethanol and Sucrose Intake in the Laboratory Mouse: Exploration Via Congenic Strains and Conditioned Taste Aversion
Authors: Blizard David A. , McClearn Gerald E. 
Published: May 2006

Background: A substantial body of literature indicates that intakes of “sweet’ solutions and ethanol are positively correlated across inbred strains of rats and mice but there has been speculation that the correlation is fortuitous and there is no agreement on the underlying mechanism.Methods and Results: We assessed the correlation between intake of sucrose and ethanol in congenic mice created by backcrossing alleles favoring sucrose intake from the BXD RI‐5 strain into DBA/2J. In addition, to probe more specifically the interrelationship between intake of the two solutions, we examined aversion generalization from sucrose to ethanol in C57BL/6J mice. Among the congenic mice, a statistically significant product‐moment correlation of r= 0.36 (p < 0.02) was found between 6‐hr intake of sucrose corrected for differences in baseline water intake and preference for 10% ethanol presented in a 96‐hr 2‐bottle test. Furthermore, C57BL/6J male mice conditioned to avoid a 0.2 M sucrose solution generalized their aversion to a 10% ethanol solution presented in the same 2‐bottle test, drinking 42.1 ± 9.38% (mean ± SE) of their total fluid intake from the ethanol tube, compared with the control group mean of 69.86 ± 8.84%.Conclusions: The positive association between intake of sucrose and ethanol in congenic mice provides strong evidence that the previously demonstrated genetic correlation between intake of these solutions is not the result of fortuitous fixation of unrelated alleles and provides suggestive evidence that, at least in the B6/D2 lineage, the genetic association between intakes of the two solutions reflects close linkage or the pleiotropic effects of the same genes. The demonstration that a conditioned taste aversion to sucrose generalized to ethanol in the C57BL/6J inbred mouse strain is an extension of similar observations in outbred rats and specifically demonstrates that intake of the two solutions is controlled by some of the same physiologic or neurological processes and thus is consistent with the pleiotropic interpretation of the genetic correlation.
P Rats Develop Physical Dependence on Alcohol Via Voluntary Drinking: Changes in Seizure Thresholds, Anxiety, and Patterns of Alcohol Drinking
Authors: Kampov‐Polevoy Alexey B. , Matthews Douglas B. , Gause Lee , Morrow A. Leslie , Overstreet David H. 
Published: May 2006

Background: It has been proposed that the alcohol‐preferring P rat meets many of the criteria for an animal model of alcoholism. However, the development of alcohol dependence has not been explored in rats that self‐administer ethanol for less than 15–20 weeks. The present study investigated the development of physical dependence upon alcohol after 2–6 weeks of voluntary alcohol intake. Changes in bicuculline‐induced seizure thresholds, microstructure of alcohol drinking, and anxiety‐related behavior were used as indices of alcohol dependence. In addition, we evaluated the microstructure of alcohol drinking associated with the development of physical dependence upon alcohol.Methods: Alcohol (10% ethanol solution) was measured in graduated drinking tubes with both alcohol and water available continuously. Microstructure of alcohol intake was monitored by a computerized drinkometer. Physical dependence upon alcohol was determined by measuring bicuculline‐induced seizure thresholds after alcohol withdrawal. Anxiety‐related behavior of P rats after alcohol withdrawal was determined by the social interaction and elevated plus maze tests.Results: Initial alcohol intake in the alcohol‐preferring P rat was relatively modest (3.9 ± 0.4 g/kg/day). Four days of forced alcohol exposure (initiation) followed by 6 weeks of voluntary drinking resulted in an increase of alcohol intake to 5.5 ± 0.2 g/kg/day. Ethanol self‐administration for 6 weeks, but not for 2 or 4 weeks, produced a significant reduction (30%; p < 0.05) in bicuculline‐induced seizure thresholds during alcohol withdrawal. Alterations in the microstructure of alcohol intake (i.e., 90% increase in the size of alcohol drinking bouts compared to the baseline [p < 0.001] with no change in bout frequency) were associated with the development of alcohol dependence. Termination of alcohol intake after 6 weeks of voluntary alcohol consumption resulted in increased anxiety according to both the social interaction and elevated plus maze tests.Conclusions: The results of this study indicate that 6 weeks of voluntary alcohol intake are sufficient for the development of physical dependence upon alcohol in the alcohol‐preferring P rats as measured by susceptibility to bicuculline‐induced seizures. This time is much shorter than the 15–20 weeks reported earlier. Development of physical dependence to alcohol was associated with an increase in daily alcohol intake (40% over the baseline), an increase in alcohol intake during each drinking bout (90% over the baseline), and elevated anxiety during alcohol withdrawal.
MK‐801 Blocks the Development of Behavioral Sensitization to Ethanol
Authors: Camarini Rosana , Frussa‐Filho Roberto , Monteiro Maristela Goldnadel , Calil Helena Maria 
Published: May 2006

Background: Studies have indicated that MK‐801 (a noncompetitive N‐methyl‐d‐aspartate receptor antagonist) participates in the long‐term neural changes responsible for sensitization to stimulant drugs. It is known that repeated administration of low doses of ethanol sensitizes animals to its stimulant effect. In this work we investigated whether MK‐801 alters the development of behavioral sensitization to ethanol.Methods: Groups of male Swiss mice were treated with saline or ethanol (2.0 g/kg) plus saline or MK‐801 (0.25 mg/kg) for 21 days. On day 25, all animals received an ethanol challenge injection (2.0 g/kg). We measured locomotor activity on days 1, 7, 14, 21 and 25. In addition, we assessed the effects of different doses of MK‐801 on the response to a low dose of ethanol (2.0 g/kg).Results: Ethanol‐treated mice developed sensitization to the locomotor‐stimulating effect of the drug, whereas those concomitantly receiving ethanol and MK‐801 did not. All doses of MK‐801 that were used stimulated the locomotor activity of both ethanol and saline‐treated animals.Conclusions: The findings support the hypothesis that N‐methyl‐d‐aspartate receptors have an important role in the development of sensitization to drugs of abuse.
Effect of Ethanol on Brain Metallothionein in Transgenic Mice
Authors: Suzuki Yutaka , Cherian M. George 
Published: May 2006

Background: Three isoforms of metallothionein (MT‐I, ‐II, and ‐III) have been detected in mice brain but little is known on their inducibility. Therefore, changes in MT levels in brain were investigated in MT‐I overexpressing transgenic mice (MT‐I*) and wild type mice of the same strain (C57BL/6J) after oral administration of ethanol.Methods: All experimental mice were given 4 g/kg of ethanol by gastric intubation. In addition, to account for the stress of animal handling, both groups of mice (MT‐I* and C57) were given distilled water by gastric intubation and used as controls. At different times after ethanol/water treatment, the mice were killed and the brains were dissected into six regions. The total amount of MT in the brain and different regions were measured by a cadmium‐binding assay. Zinc and copper were measured by atomic absorption spectrometry. The results were compared with untreated mice and corresponding control mice.Results: In C57BL/6J mice, the whole brain MT was increased by ∼1.29‐fold at 12 hr and ∼1.27‐fold at 18 hr after ethanol administration compared with basal levels. In MT‐I* male mice, the whole brain MT was increased by ∼1.64‐fold at 12 hr and ∼1.62‐fold at 18 hr after ethanol administration, whereas in MT‐I* female mice, it was increased by ∼1.57‐fold at 12 hr and ∼1.57‐fold at 12 hr and ∼61‐fold at 18 hr after ethanol administration. Although the zinc and copper levels in the whole brain were not altered, the zinc level in the cerebellum at 12 and 18 hr in male and female MT‐I* mice were increased, and zinc levels in the hippocampus of male MT‐I* mice were increased at 12 and 18 hr after ethanol treatment.Conclusions: Acute or chronic ethanol administration can cause generation of oxygen free radical and oxidative stress to the brain. The generation of free radicals is thought to be one of the causes of cell injury after ethanol administration. The mechanism of induction of MT in brain after oral ethanol administration may be associated with oxidative stress caused by ethanol or its metabolites, and can be considered as a protective mechanism against ethanol toxicity.
Impaired Protein Synthesis Induced by Acute Alcohol Intoxication Is Associated With Changes in eIF4E in Muscle and eIF2B in Liver
Authors: Lang Charles H. , Frost Robert A. , Kumar Vinayshree , Wu Duanqing , Vary Thomas C. 
Published: May 2006

Background: Acute alcohol intoxication in rats decreases protein synthesis in skeletal muscle and, to a lesser extent, in liver. The purpose of the present study was to examine potential mechanisms for the inhibitory effect of acute ethanol exposure.Methods: Rats were injected intraperitoneally with either ethanol (75 mmol/kg) or saline, and tissues were examined 2.5 hr later. Rates of protein synthesis in vivo were determined by [3H]phenylalanine incorporation into protein, and various eukaryotic initiation factors (eIFs) were quantitated by Western blot analysis to identify possible mechanisms for regulating translation.Results: Protein synthesis in gastrocnemius and liver was decreased (39% and 21%, respectively) after alcohol administration, compared with saline‐injected control animals. Alcohol administration did not alter tissue RNA content but diminished translational efficiency in muscle (43%) and liver (24%). Hepatic eIF2B activity was decreased 24% in alcohol‐treated rats, and this was associated with a 95% increase in eIF2α phosphorylation. However, alcohol did not alter the amount of 4E‐binding protein 1 (4E‐BP1) bound to eIF4E, eIF4E bound to eIF4G, or the phosphorylation state of either 4E‐BPI or eIF4E. In contrast to liver, neither eIF2B activity nor the phosphorylation of eIF2α was affected in muscle of alcohol‐treated rats. However, acute alcohol intoxication increased binding of 4E‐BP1 to eIF4E (113%), decreased the amount of eIF4E bound to eIF4G (81%), and decreased the amount of 4E‐BP1 in the phosphorylated γ‐form (77%). The plasma concentrations of insulin and insulin‐like growth factor‐I were unchanged by alcohol, but muscle insulin‐like growth factor‐I messenger ribonucleic acid abundance was decreased 35%.Conclusions: These data suggest that acute alcohol intoxication decreases translation initiation and protein synthesis in liver and muscle via different mechanisms. Changes in eIF2B appear to predominate in liver, whereas alterations in eIF4E availability appear more critical in skeletal muscle for controlling translation initiation.
Involvement of μ‐Opioid Receptor in the Salsolinol‐Associated Place Preference in Rats Exposed to Conditioned Fear Stress
Authors: Matsuzawa Shigeki , Suzuki Tsutomu , Misawa Miwa 
Published: May 2006

Background: Salsolinol, a condensation product of dopamine with acetaldehyde (the initial oxidation product of ethanol), has long been discussed as an endogenous opioid system‐activating factor contributing to the etiology of alcoholism. Moreover, psychological stress has been considered to play an important role in the development of alcoholism.Methods: Male Sprague Dawley rats were subjected to conditioned fear stress (at 24 hr after electric footshock exposure), and then salsolinol or saline was injected intraperitoneally. For conditioning, rats were immediately confined to the nonpreferred compartment after salsolinol injection and to the preferred compartment after saline injection on alternate days. This conditioning session was repeated twice daily (for 8 days). Test session was carried out 1 day after the last conditioning session.Results: Salsolinol [10 mg/kg, but not 1, 3 or 30 mg/kg, intraperitoneally (ip)] without conditioned fear stress induced a slight, but significant, place preference. In contrast, salsolinol (1, 3, and 10 mg/kg, ip) with conditioned fear stress induced a marked and significant place preference. The nonselective opioid receptor antagonist naloxone hydrochloride (which can pass into the brain), but not the nonselective peripheral opioid receptor antagonist naloxone methiodide (which cannot pass into the brain), significantly attenuated the salsolinol (3 mg/kg, ip)‐induced place preference under conditioned fear stress. Moreover, the selective μ‐opioid receptor antagonist β‐funaltrexamine significantly attenuated the salsolinol‐induced place preference. Furthermore, 0.3 mg/kg salsolinol (which produced no significant place preference) combined with the μ‐opioid receptor agonist morphine [0.1 mg/kg, subcutaneously (sc)], at the dose which alone produced no significant place preference, produced a marked and significant place preference. Both naloxone hydrochloride and β‐funaltrexamine significantly attenuated the salsolinol plus morphine‐induced place preference.Conclusions: Salsolinol may have some rewarding effect, and its rewarding effect may be potentiated by psychological stress. In addition, the rewarding effect of salsolinol especially under psychological stress may involve the endogenous central opioid system, i.e., μ‐opioid receptor.
A Behavioral Economic Analysis of Concurrent Ethanol‐ and Water‐Reinforced Responding in Different Preference Conditions
Authors: Williams Keith L. , Woods James H. 
Published: May 2006

Background: The reinforcing properties of orally self‐administered drugs have been evaluated by using choice procedures. The preference for the drug over a nondrug alternative has indicated that the drug has greater value than the nondrug alternative as a reinforcer at some drug concentrations. However, at large drug concentrations, the fluid deliveries of the drug may be equal to or less than those of the nondrug alternative, whereas the actual drug intake (milligrams per kilogram of body weight) may continue to increase. In this study, we used behavioral economics to evaluate the reinforcing strength of ethanol in conditions where baseline ethanol fluid deliveries were greater than, equal to, or less than those of the concurrently available water.Methods: Four male rhesus monkeys were allowed access to ethanol (2%, 8%, or 32%) and water for 2 hr/day under a fixed ratio (FR) 4 reinforcement schedule. At each ethanol concentration, the FR for both fluids was gradually increased to FR 64.Results: During the FR 4 schedule, the fluid deliveries of ethanol at 2%, 8%, and 32% were greater than, equal to, and less than those of water, respectively. When the FR was increased at 2% ethanol, fluid deliveries and responding decreased for both the ethanol and water. When the FR was increased at 8% ethanol, water fluid deliveries and responding decreased more rapidly than did those of ethanol. When the FR was increased at 32% ethanol, the ethanol fluid deliveries remained the same across all FRs, whereas water fluid deliveries decreased rapidly. At 8% and 32% ethanol, the responding for ethanol, relative to water, increased dramatically.Conclusions: In behavioral economic terms, demand for ethanol was more inelastic regardless of whether the ethanol or water maintained more absolute fluid deliveries at baseline FRs. Therefore, researchers should examine the reinforcing effects of ethanol in a variety of concentration and schedule conditions rather than drawing inferences regarding reinforcing effects simply based on a preference measure.
Tolerance to Acute Ethanol Inhibition of Peptide Hormone Release in the Isolated Neurohypophysis
Authors: Knott Thomas K. , Dayanithi Govindan , Coccia Vincent , Custer Edward E. , Lemos José R. , Treistman Steven N. 
Published: May 2006

Background:Acute ethanol (EtOH) exposure reduces the evoked release of vasopressin (AVP) and oxytocin (OT) from excised neurohypophyses and from dissociated neurohypophysial terminals of the rat.Methods and Results:Rats placed on a diet that maintained blood levels of 30 mM EtOH for 20 to 40 days developed tolerance to acute EtOH inhibition of release. In the presence of 10 mM EtOH, high (50 mM) K+‐induced release of AVP from isolated neurohypophysial terminals of EtOH‐naive rats was reduced by 77.7 ± 1.4%, whereas in the chronic EtOH group, release was reduced by only 9.4 ± 8.7%. Similar tolerance was evident during acute challenge with 75 mM EtOH, as well as for release of OT from isolated terminals. Animals treated with an intraperitoneal injection of EtOH and sacrificed 90 min postinjection did not exhibit the reduced EtOH inhibition of release from dissociated terminals during a 75 mM EtOH acute challenge.Conclusions:The altered component responsible for the tolerance to inhibition of release resides in the isolated terminal, because tolerance measured in vitro from intact neurohypophyses was similar to that seen in isolated terminals. The failure of EtOH‐injected animals to exhibit reduced inhibition of release in response to an acute EtOH challenge indicates that short‐term elevated blood alcohol level does not induce this tolerance. The finding of tolerance to EtOH‐induced inhibition of release from the intact neurohypophysis and isolated terminals provides a physiological preparation in which to examine the molecular targets of acute drug action modified after chronic exposure to the drug.
Effects of Fetal Ethanol Exposure on Pituitary‐Adrenal Sensitivity to Secretagogues
Authors: Osborn J. A. , Yu C , Stelzl G. E. , Weinberg J. 
Published: May 2006

Background: Rodents prenatally exposed to ethanol demonstrate hormonal hyper‐responsiveness to stressors in adulthood. The present study examined the hypothesis that an increased sensitivity of the adrenal to ACTH and/or the pituitary to corticotropin releasing hormone (CRH) after dexamethasone suppression, may play a role in the hormonal hyper‐responsiveness seen in fetal ethanol‐exposed rats.Methods: Sprague‐Dawley males and females from prenatal ethanol‐exposed (E), pair‐fed (PF), and ad libitum‐fed control (C) groups were tested in adulthood (90‐120 days). Testing was done in a series of two experiments carried out during the trough of the corticosterone rhythm, the time of greatest sensitivity to feedback inhibition. Twenty‐four to 48 hr before testing, jugular cannulae were implanted for hormone infusion and blood sample collection. In both experiments, animals were injected intraperitoneally with dexamethasone‐21‐phosphate (DEX) (15 μg/100 g body weight for males or 30 μg/100 g body weight for females) 3 hr before testing to suppress endogenous hypothalamic‐pituitary‐adrenal (HPA) activity. Animals were given a bolus infusion of ACTH (0‐0.10 mg/rat) and blood samples (0.2 cc) were drawn at 60‐min intervals over 240 min for determination of plasma corticosterone (CORT) levels (Experiment 1), or were given a bolus infusion of CRH (0‐20 μg/kg body wt) and samples drawn at 0, 5, 15, and 30 min for determination of plasma ACTH and CORT levels (Experiment 2).Results: As expected, sex differences in adrenal response to ACTH and pituitary response to CRH were observed; females had higher CORT and ACTH levels than males at all concentrations of ACTH and CRH. In addition, dose‐response relationships between exogenously administered ACTH or CRH and plasma CORT were demonstrated; increasing concentrations of secretagogues resulted in higher and/or more prolonged CORT responses in both males and females. There were no significant differences among E, PF, and C males or females in adrenal sensitivity to ACTH. However, prenatal ethanol exposure altered pituitary sensitivity to CRH in both males and females. E and PF mmales demonstrated increased plasma ACTH but not CORT compared with C males, wwhereas E females demonstrated increased plasma ACTH and CORT levels compared with PF and C females after CRH infusion.Conclusions: Together these data suggest that (1) E animals do not show increased adrenal sensitivity to ACTH compared with controls; (2) the insult of prenatal ethanol exposure may result in altered pituitary sensitivity to CRH after DEX suppression; and (3) there may be a sex‐specific difference in sensitivity of the mechanism(s) underlying HPA hyper‐responsiveness.