bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic Ethanol Consumption Enhances Interleukin‐1‐Mediated Signal Transduction in Rat Liver and in Cultured Hepatocytes
Authors: Valles Soraya L. , Blanco Ana M. , Azorin Inmaculada , Guasch Rosa , Pascual María , Gomez‐Lechon María Jose , Renau‐Piqueras Jaime , Guerri Consuelo 
Published: December 2003

Background: Interleukin‐1 (IL‐1) is a central mediator of the inflammatory process. Increased serum levels of IL‐1 have been reported in alcoholics with liver damage, but it remains unknown whether chronic ethanol intake, in the presence or absence of lipopolysaccharide (LPS), activates IL‐1 release and signaling in the hepatocyte.Methods: IL‐1β and IL‐10 release, expression of their receptors (IL‐1RI and IL‐10R), and the IL‐1RI signal transduction response were evaluated in livers and cultured hepatocytes from ethanol‐fed or pair‐fed rats exposed in vivo or in vitro to LPS, ethanol, or both.Results: Chronic ethanol intake increased both the serum levels of IL‐1β and IL‐10 and the expression of IL‐1RI, but not of IL‐10R, in the liver microsomal fraction. In vivo LPS administration potentiated the ethanol‐induced release of plasma cytokines. It is interesting to note that ethanol, either given in a single dose or chronically fed, stimulated IL‐1β and IL‐10 release from cultured hepatocytes. Stimulation of hepatocytes with IL‐1β caused a higher activation of IL‐1‐associated kinase, extracellular receptor‐activated kinases 1 and 2, and nuclear factor‐κB (NF‐κB) in hepatocytes from alcohol‐fed animals than from controls. Furthermore, in the absence of any stimulation, hepatocytes from alcohol‐fed animals showed an activation of both kinases, as well as an increase in NF‐κB binding. Our results suggest the participation of the extracellular signal‐regulated kinase (ERK)1/2 pathway in ethanol‐induced NF‐κB activation, because treatment with PD‐98059, an ERK1/2 inhibitor, partially suppressed IL‐1β‐induced NF‐κB expression.Conclusions: Chronic ethanol intake potentiates the action of the proinflammatory cytokine IL‐1β, enhancing the release and signaling response of IL‐1β in the hepatocyte, which in conjunction with other cytokines or LPS may exacerbate the inflammatory damage associated with alcoholic liver disease.
Altered Affective Modulation of the Startle Reflex in Alcoholics With Antisocial Personality Disorder
Authors: Miranda Robert , Meyerson Lori A. , Myers Ryan R. , Lovallo William R. 
Published: December 2003

Background: Individual differences in neural circuitry that regulate emotional reactivity may be associated with alcoholism and antisocial personality disorder (ASPD), a common comorbid condition. The emotion‐modulated startle reflex was used to investigate emotional reactivity among alcohol‐dependent (AD) men with and without ASPD.Methods: Sixty‐two men were tested: (1) AD (n= 24), (2) AD‐ASPD (n= 17), and (3) non‐AD, non‐ASPD controls (n= 21). Participants completed self‐report instruments and clinical interviews and had eye‐blink electromyograms measured in response to acoustic startle probes while viewing color photographs rated as affectively pleasant, neutral, and unpleasant.Results: Startle blink magnitudes were larger during unpleasant as compared with pleasant slides for control and AD groups, resulting in significant linear trend effects (p < 0.001) and nonsignificant quadratic trend effects. In contrast, AD‐ASPD did not show a significant difference in blink magnitude during unpleasant and pleasant slides and did not show a significant linear valence trend or quadratic trend effect (p > 0.6). Subjective valence and arousal ratings of the photographs were similar across groups.Conclusions: Adult male alcoholics with ASPD have abnormal emotional responsiveness to both pleasant and unpleasant stimuli relative to alcoholics without ASPD and to controls.
Chronic Ethanol Consumption by C57BL/6 Mice Promotes Tolerance to Its Interoceptive Cues and Increases Extracellular Dopamine, an Effect Blocked by Naltrexone
Authors: Middaugh Lawrence D. , Szumlinski Karen K. , Van Patten Yancy , Marlowe Angela‐Leigh Bandy , Kalivas Peter W. 
Published: December 2003

Background: C57BL/6 (B6) mice voluntarily consume ethanol. Although preingestive factors might be accountable, the fact that B6 mice voluntarily consume sufficient ethanol to set the conditions for an ethanol‐deprivation effect suggest that post‐ingestive pharmacological induced changes also occur. In this study, we determined the amounts of ethanol voluntarily consumed by B6 mice and associated blood ethanol levels (BEL), the effects of this consumption on extracellular dopamine (DA) and how this was altered by naltrexone, as well as on its interoceptive discriminative cues.Methods: In experiment 1, the amounts of 12% ethanol consumed at 2, 4, and 6 hr into the active phase of the circadian cycle and associated BEL were determined. In experiment 2, dialysate samples were collected for 1 hr to establish basal DA levels. Mice were then injected with saline or naltrexone (6 mg/kg) and given access to water and 12% ethanol or to water only, and samples were collected at 20‐min intervals for the next 2 hr. In experiment 3, mice were trained to discriminate ethanol's interoceptive cues via operant techniques, and half were given 3 weeks access to ethanol and water, the other half water only. Ethanol‐consuming and water control mice were again tested for their ability to discriminate the drug's interoceptive cues.Results: Mice ingested nearly 6 g/kg of ethanol and attained BEL near 100 mg/100 mL by 6 hr into the active phase. Ethanol intake at 2‐hr into the dark phase was approximately 2.5 g/kg, and increased DA to approximately 100% above basal levels. Naltrexone reduced ethanol consumption and blocked the DA increase. Ethanol consumption for 3 weeks attenuated its discriminative cues.Conclusions: B6 mice voluntarily consume sufficient ethanol (1) to produce intoxicating BEL; (2) to increase DA levels in nucleus accumbens, an effect blocked by naltrexone; and (3) to attenuate its discriminative cues.
A Mouse Model of Prenatal Ethanol Exposure Using a Voluntary Drinking Paradigm
Authors: Allan Andrea M. , Chynoweth Julie , Tyler Lani A. , Caldwell Kevin K. 
Published: December 2003

Background: The incidence of fetal alcohol spectrum disorders is estimated to be as high as 1 in 100 births. Efforts to better understand the basis of prenatal ethanol‐induced impairments in brain functioning, and the mechanisms by which ethanol produces these defects, will rely on the use of animal models of fetal alcohol exposure (FAE).Methods: Using a saccharin‐sweetened alcohol solution, we developed a free‐choice, moderate alcohol access model of prenatal alcohol exposure. Stable drinking of a saccharin solution (0.066%) was established in female mice. Ethanol then was added to the saccharin in increasing concentrations (2%, 5%, 10% w/v) every 2 days. Water was always available, and mice consumed standard pellet chow. Control mice drank saccharin solution without ethanol. After a stable baseline of ethanol consumption (14 g/kg/day) was obtained, females were impregnated. Ethanol consumption continued throughout pregnancy and then was decreased to 0% in a step‐wise fashion over a period of 6 days after pups were delivered. Characterization of the model included measurements of maternal drinking patterns, blood alcohol levels, food consumption, litter size, pup weight, pup retrieval times for the dams, and effects of FAE on performance in fear‐conditioned learning and novelty exploration.Results: Maternal food consumption, maternal care, and litter size and number were all found to be similar for the alcohol‐exposed and saccharin control animals. FAE did not alter locomotor activity in an open field but did increase the time spent inspecting a novel object introduced into the open field. FAE mice displayed reduced contextual fear when trained using a delay fear conditioning procedure.Conclusions: The mouse model should be a useful tool in testing hypotheses about the neural mechanisms underlying the learning deficits present in fetal alcohol spectrum disorders. Moreover, a mouse prenatal ethanol model should increase the opportunity to use the power of genetically defined and genetically altered mouse populations.
Effects of Alcohol Withdrawal on 24 Hour Ambulatory Blood Pressure Among Alcohol‐Dependent Patients
Authors: Estruch Ramón , Sacanella Emilio , De la Sierra Alejandro , Aguilera María Teresa , Antúnez Emília , Nicolás José M. , Fernández‐Solá Joaquín , Coca Antonio , Urbano‐Márquez Álvaro 
Published: December 2003

Background: Although epidemiologic studies have reported an association between alcohol intake and high blood pressure (BP), the results of intervention studies have shown inconsistent results. We embarked on a study to determine whether different subgroups of alcohol‐dependent patients may be identified in relation to the effect of alcohol on BP.Methods: Fifty alcohol‐dependent men (mean age, 41.4 years) received 0.4 g of ethanol per kilogram of body weight every 4 hr in 200 ml of orange juice during 24 hr and the same amount of orange juice without ethanol during another 24 hr. Twenty‐four hour ambulatory BP monitoring was performed during ethanol and orange juice intakes, as was hormonal and biochemical analysis.Results: Thirty‐five (75%) alcohol‐dependent men were normotensive and 15 (30%) hypertensive. Eighteen (51%) normotensive and 12 (80%) hypertensive subjects showed a significant decrease in 24 hr mean BP after ethanol withdrawal (mean decrease of 8.4 mm Hg [95% confidence interval, −11.2 to −5.7] and 12.5 mm Hg [confidence interval, −16.2 to −8.8], respectively) and were considered as sensitive to alcohol. The remaining alcohol‐dependent subjects were considered as resistant to alcohol. Normotensive subjects sensitive to ethanol showed a significantly greater left ventricular mass and a significantly lower ejection fraction than those normotensive patients whose BP did not change after ethanol withdrawal (both p < 0.01).Conclusions: More than three fourths of the hypertensive and more than half of the normotensive alcohol‐dependent patients showed sensitivity to the pressor effects of ethanol. Impairment also was observed in heart function in normotensive patients sensitive to the pressor effects of ethanol.
Neurokinin Type‐3 Receptor Stimulation Impairs Ethanol‐Associated Appetitive Behavior in Wistar Rats
Authors: Slawecki Craig J. , Roth Jennifer 
Published: December 2003

Objectives: Stimulating central neurokinin type‐3 (NK‐3) receptors decreases ethanol intake in rats. Although paraventricular nucleus of the hypothalamus (PVN) has a high density of NK‐3 receptors, their influence on ethanol reinforcement has not been examined. This study's purpose was to assess the effects of intra‐PVN infusion of senktide, a NK‐3 receptor agonist, on ethanol self‐administration. In a follow‐up study, senktide's effects on ethanol self‐administration after intracerebroventricular (ICV) infusion were examined.Methods: Male Wistar rats were trained to self‐administer 10% ethanol (10E) in the “Sipper Tube” model described by Samson and colleagues, Guide cannula were then aimed bilaterally at the PVN or unilaterally at the lateral cerebral ventricle. Intra‐PVN (5–100 ng/side) or ICV (30–500 ng/rat) effects of senktide on 10E self‐administration were also examined as a preliminary test of senktide's selectivity.Results: Intra‐PVN and ICV infusion of senktide reduced the average number of consecutive lever presses and increased the time taken to complete the lever press requirement when 10E served as the reinforcer. Increased duration of the lever‐pressing component was observed when senktide was administered prior to 2S self‐administration sessions. Neither PVN nor ICV senktide administration significantly altered 10E or 2S consumption.Conclusions: These data suggest that stimulation of central neurokinin typ‐3 receptors in the Wistar rat reduces appetitive behavior while having little or no impact on consummatory behavior. Ethanol “seeking” appeared more sensitive to disruption by senktide than sucrose “seeking.” However, further studies assessing the senktide's effects on sucrose‐maintained behavior are needed to verify this hypothesis. Lastly, it is hypothesized that lack of effect of senktide on intake is in part related to the use of outbred Wistar rats in these studies instead of selectively bred rats.
The Effects of Affective, Behavioral, and Cognitive Components of Trait Anger on the Alcohol‐Aggression Relation
Authors: Giancola Peter R. , Saucier Donald A. , Gussler‐Burkhardt Natasha L. 
Published: December 2003

Objective: The purpose of this study was to investigate the effects of affective, behavioral, and cognitive components of trait anger on alcohol‐related aggression in men and women.Methods: Subjects were 300 (150 men and 150 women) healthy social drinkers between 21 and 35 years of age. Trait anger was measured using the ABC Anger Inventory. Following the consumption of either an alcohol or a placebo beverage, subjects were tested on a modified version of the Taylor Aggression Paradigm in which mild electric shocks were received from, and administered to, a fictitious opponent during a competitive task. Aggressive behavior was operationalized as the shock intensities administered to the fictitious opponent under conditions of low and high provocation.Results: Results indicated that alcohol increased aggression only for men with higher behavioral and cognitive anger scores and only for women with higher behavioral anger scores. Results also showed that when all anger components were taken into account, behavioral anger was the only factor that put one at risk for intoxicated aggression.Conclusions: Two recent studies demonstrated that the trait of “general” anger is a risk factor for intoxicated aggression (Giancola, 2002a; Parrott and Zeichner, 2002). The present investigation confirmed and extended these findings by examining the role of three different components of anger. The results highlight the fact that alcohol consumption does not increase aggression in all persons and in all situations. An important goal for future research is to identify which individual difference and contextual factors are most important in determining who will, and will not, behave in an aggressive manner when intoxicated.
α4β2* Nicotinic Acetylcholine Receptors Modulate the Effects of Ethanol and Nicotine on the Acoustic Startle Response
Authors: Owens Jeremy C. , Balogh Seth A. , McClure‐Begley Tristan D. , Butt Christopher M. , Labarca Cesar , Lester Henry A. , Picciotto Marina R. , Wehner Jeanne M. , Collins Allan C. 
Published: December 2003

Background: Ethanol modulates the functional activity of α4β2 neuronal nicotinic cholinergic receptors (nAChR) when measured in vitro, but the potential role of α4β2 nAChRs in regulating behavioral effects of ethanol is unknown. Recently, Tritto et al. (Tritto T, Stitzel JA, Marks MJ, Romm E, Collins AC (2002) Variability in response to nicotine in the LS×SS RI strains: potential role of polymorphisms in alpha4 and alpha6 nicotinic receptor genes. Pharmacogenetics 12:197–208) reported that a polymorphism (A529T) in the α4 nAChR subunit gene is associated with variability in nicotine's effects on startle in the LS×SS recombinant inbred (RI) strains. Ethanol also alters the acoustic startle response. Thus, we evaluated the potential role of α4β2 nAChRs in modulating ethanol's effects on acoustic startle.Methods: The effects of ethanol on acoustic startle were determined in the LS×SS RI strains. In addition, the effects of ethanol and nicotine were also measured in α4 gain of function and β2 null mutant mice. The β2 mutants do not express the major variant of α4 nAChRs, α4β2.Results: An association between the α4 A529T polymorphism and ethanol's effects on startle was found in the LS×SS RI strains; those strains that express the A529 variant of α4 were more sensitive to ethanol‐induced depression of startle. The α4 gain of function mutants were more sensitive to the effects of both nicotine and ethanol and the β2 null mutants were less sensitive to both drugs.Conclusions: α4β2‐containing nAChRs may play important roles in modulating the effects of both ethanol and nicotine on the acoustic startle response. We suggest that nAChR subunit genes should be evaluated as potential contributors to both alcoholism and tobacco abuse.
Pain Thresholds in Alcohol Preferring and Non‐preferring Rats: Diurnal and Repeated Trial Line Differences
Authors: Kimpel Mark W. , Brown Matthew M. , Froehlich Janice C. 
Published: December 2003

Background: Studies in humans and animals suggest that those with a genetic predisposition toward high levels of alcohol consumption have decreased pain thresholds. The present study explores this association in rat lines selectively bred for alcohol preference or nonpreference.Methods: 13 HAD1, 11 LAD1, 16 iP5C, and 16 iNP1 rats were tested in the Ugo Basile Plantar Analgesiometer and the IITC Tail Flick device. Five trials were conducted in each test session with one session per device conducted in the light and one in the dark. Trial one latency represents baseline latency. Decline in Latency over Repeated Trials (DLRT) was analyzed using linear regression.Results: Testing in the Plantar Analgesiometer revealed no significant line differences in baseline latency (iP5C versus iNP1; HAD1 vs. LAD1). The alcohol preferring lines (iP5C and HAD1), however, both demonstrated an increase in baseline latency in the dark phase compared to the light phase (p < 0.05). The iNP1 line demonstrated highly significant DLRT in both the light phase (p < 0.001) and dark phase (p < 0.01) while the iP5C line demonstrated a significant DLRT only at night (p < 0.01). In the tail flick apparatus, the HAD1 line demonstrated a significantly increased baseline latency compared to the LAD1 line in both the light (p < 0.05) and dark (p < 0.01) phases. The HAD1 line also demonstrated a significant increase in baseline latency in the dark compared to the light phase (p < 0.05) and a significant DLRT in the light (p < 0.01) and the dark phase (p < 0.001).Conclusions: The alcohol preferring HAD1 line demonstrates a significantly increased baseline tail latency compared to the nonpreferring LAD1 line in both light and dark phases. There is a significant diurnal rhythm of paw and tail latency in both of the alcohol preferring lines (iP5C and HAD1) but not in the nonpreferring lines (iNP1 and LAD1). A novel finding of Decline in Latency with Repeated Trials (DLRT) was found in both alcohol preferring and nonpreferring lines; degree of DLRT differed as a function of line and circadian period.
Developmental Differences in the Sensitivity of Hippocampal GABAA Receptor‐Mediated IPSCS to Ethanol
Authors: Li Qiang , Wilson Wilkie A. , Swartzwelder H.S. 
Published: December 2003

Background: Ethanol consumption by juveniles and adolescents is a public health problem of massive proportions. Recent studies have indicated that adolescents may be less sedated by ethanol than adults, and may thus be able to consume more ethanol, putting them at greater risk for ethanol addiction and other negative consequences of ethanol use. However, the mechanisms underlying this developmental difference are unknown. One contributing factor may be GABAA receptor‐mediated inhibition, which is known to produce sedation. Ethanol is known to enhance this inhibitory process.Methods: Using whole cell recording, we tested the response of GABAA receptor‐mediated IPSCs in brain slices of rat hippocampus from animals representing three developmental stages: juvenile, early adolescent, and adult.Results: We found significantly greater ethanol‐induced enhancement of GABA‐mediated IPSPs in cells from adult animals compared to those from juvenile or adolescent animals.Conclusions: We conclude that the sensitivity of GABAA receptor‐mediated inhibitory processes to ethanol increases with development from the juvenile period to adulthood.
Effects of prey quality on social wasps when given a choice of prey
Authors: Stamp N.E. , Meyerhoefer B. 
Published: December 2003

AbstractThe effect of prey quality on foraging behavior and colony demographics of the social wasp Polistes fuscatus was examined by providing a choice between non‐toxic prey (Manduca sexta caterpillars) and sublethally toxic prey (Junonia coenia caterpillars), and then comparing the performance of these colonies to others given only the non‐toxic prey. In the choice, one of two types of Manduca were used: those fed an artificial diet or those fed plantain (Plantago lanceolata), which contains iridoid glycosides (IGs) that Junonia coenia store but which Manduca does not. Despite the negative correlation between the number of Junonia prey used and number of adult offspring produced, when a surplus of non‐toxic prey was available, the wasps did not completely avoid the toxic prey. However, they were more discriminating when the choice was between Manduca fed an artificial diet and Junonia fed plantain vs. when both prey species had eaten the plantain. Because the wasps had a choice of prey types and had a surplus of prey on about one‐third of the days, the wasps were able to take enough non‐toxic prey to avoid some of the negative consequences of IGs. For example, the total number of wasp offspring per nest was not affected, but mean weight of female offspring per colony was less for colonies given both prey types eating plantain, compared to that for colonies fed only non‐toxic prey, or those given a choice of non‐toxic prey vs. toxic prey. In addition, compared to the control (only non‐toxic prey), the proportion of males produced was less in the treatment that provided a clear contrast between non‐toxic and toxic prey. Why these wasps did not avoid the toxic prey is discussed.
Barley yellow dwarf virus, wheat, and Sitobion avenae: a case of trilateral interactions
Authors: Fiebig M. , Poehling H.‐M. , Borgemeister C. 
Published: December 2003

AbstractWe analysed interactions in the system of two Barley Yellow Dwarf Virus (BYDV) strains (MAV and PAV), and wheat (cv. Tinos) as host plant for the virus, and the cereal aphid Sitobion avenae (F.) as vector, in particular whether or not infection by the virus might alter host plant suitability in favour of vector development. By measuring the amino acid and sugar content in the phloem sap of infected and non‐infected wheat plants we found a significant reduction in the concentration of the total amount of amino acids on BYDV‐infected plants. Qualitative and quantitative analysis of honeydew and honeydew excretion indicated a lower efficiency of phloem sap utilisation by S. avenae on infected plants. In addition, S. avenae excreted less honeydew on infected plants. Both BYDV strains significantly affected aphid development by a reduction in the intrinsic rate of natural increase. Hence, infection by the virus reduced the host suitability in terms of aphid population growth potential on BYDV‐infected plants. However, more alate morphs developed on virus‐infected plants. These findings are discussed in relation to the population dynamics of S. avenae, and, as a consequence, the spread of BYDV.