bluuebunny/crossref_metadata_2025_split huggingface dataset:
Basis of Variable Sensitivities of GABAAReceptors to Ethanol
Authors: Mori Takashi , Aistrup Gary L. , Nishikawa Kiyonobu , Marszalec William , Yeh Jay Z. , Narahashi Toshio 
Published: May 2006

Background:The GABAAsystem is believed to be one of the crucial target sites for ethanol. However, in the literature, data using various preparations yielded controversial conclusions regarding the ethanol potency to modulate the activity of GABAAreceptors. We have previously shown that the potency ofn‐alcohols to potentiate GABA‐induced currents is correlated with their carbon chain length. This correlation was further compared among four cell types in an attempt to explain the variable potencies of ethanol to potentiate GABA responses.Methods:Whole‐cell patch clamp experiments were performed to determine and compare the potencies ofn‐alcohols in potentiating GABA‐induced currents in rat dorsal root ganglion (DRG) neurons, human embryonic kidney cells expressing the rat α1β2γ2S or α1β2γ2L subunits, and rat cortical neurons.Results:The GABAA, receptors of the four cell types tested were all sensitive ton‐alcohols, albeit with different potencies and efficacies. The effective concentration to increase GABA‐induced currents to 125% of control (EC125) was correlated with the carbon chain length ofn‐alcohols, but slopes for this relationship are different among DRG neurons, the α1β2γ2S, and α1β2γ2L subunits. Thus, the potencies of lower alcohols such as ethanol differed among these cell types although higher alcohols such asn‐octanol were almost equally potent. In cortical neurons, however, the relationship was shifted in the direction of longer carbon chains, indicating that their sensitivity was lower than those of the other three cell types. The ethanol EC125values as obtained by experiments or those by extrapolation (in parenthesis) from the EC125‐carbon chain length relationship were: 169 (103) mM for DRG neurons, 501 (333) mM for the α1β2γ2L subunits, 781 (674) mM for the α1β2γ2S subunits, and (1897) mM for cortical neurons.Conclusions:It was concluded that the GABAAreceptors of these four cell types were basically sensitive ton‐alcohols including ethanol but the sensitivity curve was shifted to the lower side in the order of decreasing sensitivity of DRG neurons > α1β2γ2L > α1β2γ2S > cortical neurons.
Serotonergic Function, Behavioral Disinhibition, and Negative Affect in Children of Alcoholics: The Moderating Effects of Puberty
Authors: Twitchell Geoffrey R. , Hanna Gregory L. , Cook Edwin H. , Fitzgerald Hiram E. , Zucker Robert A. 
Published: May 2006

Background: Serotonergic (5‐HT) dysfunction has been implicated in both behavioral disinhibition and negative affect in adults. Although our group's previous work found decreased whole blood 5‐HT in high versus low behavior problem children of alcoholics, some child/adolescent studies report conflicting results, and 5‐HTs role in negative affect has been largely unexamined. Age‐related developmental factors may play a role in these relationships.Methods: This report is from an ongoing prospective study of the development of risk for alcohol abuse/dependence and other problematic outcomes in a sample of families subtyped by father's alcoholism classification. The present study extends previous work and examines relationships between whole blood 5‐HT and both child behavioral disinhibition (an aggression index from the Child Behavior Checklist) and negative affect (Child Behavior Checklist Anxious/Depressed scale) in offspring from 47 families (N= 45 boys and 17 girls; mean age = 10.88 ± 2.03 yr).Results: The most important finding was that puberty moderated relationships between 5‐HT and both behavioral disinhibition and negative affect with a relationship for pubescent children (n= 14, r= ‐0.54, p= 0.05;r= ‐0.57,p= 0.04, respectively) but no relationship for prepubescent children (n= 48,r= 0.05, p= 0.75; r= ‐0.15,p= 0.31, respectively).Conclusions: The moderating effects of puberty may help clarify inconsistencies in child/adolescent literature. Furthermore, there appears to be a relationship between 5‐HT and negative affect which parallels that between 5‐HT and behavioral disinhibition. Pubertal status may be an important variable to evaluate as a moderator in relation to the developmental context of the role 5‐HT dysfunction may play in various models of behavior related to alcoholism over the early life course.
Decision‐Making Biases, Antisocial Personality, and Early‐Onset Alcoholism
Authors: Mazas Carlos A. , Finn Peter R. , Steinmetz Joseph E. 
Published: May 2006

Background: Disinhibited, antisocial traits increase the risk for early‐onset alcoholism. Research also suggests that decision biases which favor immediate large rewards regardless of long‐term consequences may be important mechanisms associated with the biological substrates of antisocial traits. This study tested the hypothesis that early‐onset alcoholism with antisocial personality (ASP) would be associated with favoring immediate larger rewards despite their being associated with long‐term losses.Methods: Twenty‐seven early‐onset alcoholics with and without a diagnosis of ASP, eight subjects with ASP but no alcohol dependence, and 32 controls were tested on a task that manipulated the magnitude of immediate rewards and the magnitude of long‐term punishments. The sample was recruited from the community via advertisements.Results: Compared with subjects without ASP, subjects with ASP favored larger immediate rewards despite long‐term losses regardless of alcohol dependence; however, they learned to shift their decisions in a more advantageous direction over time. A disadvantageous decision bias also was associated with drinking greater quantities of alcohol and having a lower IQ.Conclusions: This study suggests that ASP in a young adult noninstitutionalized sample was associated with a pattern of disadvantageous decision making similar to that observed in patients with antisocial behavioral characteristics associated with lesions in the ventromedial frontal cortex. The data also suggest that this pattern of disadvantageous decision making is associated with consuming larger quantities of alcohol but not consuming alcohol more frequently.
Sertraline Treatment for Alcohol Dependence: Interactive Effects of Medication and Alcoholic Subtype
Authors: Pettinati Helen M. , Volpicelli Joseph R. , Kranzler Henry R. , Luck Gary , Rukstalis Margaret R. , Cnaan Avital 
Published: May 2006

Background: Characteristic behaviors of some alcohol‐dependent individuals, e.g., binge drinking, comorbid psychopathology, and some types of alcohol‐related problems, have been linked to abnormalities in serotonergic neurotransmission. However, studies that have evaluated serotonergic pharmacotherapy for reducing drinking have yielded conflicting results. One explanation for these findings is a general failure to distinguish alcohol subgroups that may be differentiated on the basis of serotonergic abnormalities. However, in 1996, Kranzler and colleagues reported that Type B alcoholics, who are characterized by high levels of premorbid vulnerability, alcohol dependence severity, and comorbid psychopathology, showed less favorable drinking outcomes in response to treatment with fluoxetine, a serotonin reuptake inhibitor, than with placebo. This medication effect was not seen in Type A alcoholics, i.e., those with lower risk/severity of alcoholism and psychopathology. The aim of the present study was to explore the validity of differential responding by alcohol‐dependent subtypes using the serotonin reuptake inhibitor, sertraline.Methods: A k‐means clustering procedure was applied to a sample of alcohol‐dependent subjects enrolled in a 14‐week, placebo‐controlled trial of 200 mg/day of sertraline, classifying them into lower‐risk/severity (Type A: n= 55) and higher‐risk/severity (Type B: n= 45) subgroups.Results: A significant interaction between alcoholic subtype and medication condition was found, confirming the findings of Kranzler and colleagues that alcoholic subtypes responded differentially to serotonergic medication. Somewhat at variance with their results, however, the present study showed that the lower risk/severity (Type A) subjects had more favorable outcomes when treated with sertraline compared to placebo.Conclusions: Alcoholic subtypes differentially responded to sertraline when used as a treatment to reduce alcohol drinking, with one subtype having more favorable outcomes. Subtyping alcoholics may help to resolve conflicting findings in the literature on serotonergic treatment of alcohol dependence.
Hospital Morbidity of Alcohol Use Disorders in the Center of France
Authors: Reynaud Michel , Malet Laurent , Facy Françoise , Glanddier Phyllis 
Published: May 2006

Background: The Auvergne region of central France has the third highest mortality rate in the country for alcohol‐related disorders and the highest level of alcohol consumption among young people.Methods: An exhaustive cross‐sectional study of regional hospital morbidity related to alcohol was undertaken on a single day in May 1998, including 9,552 hospital beds. All inpatients age 16 and older in the Departments of Medicine, Surgery, Obstetrics and Gynecology, Psychiatry, and Medium‐Stay Services were studied. The aim was to define alcohol‐related behavior patterns (by using the Diagnostic and Statistical Manual of Mental Disorders [DSM‐IV] criteria of abuse and dependence and the CAGE questionnaire) and to measure the proportion of nonsomatic alcohol‐related care dispensed in hospital.Results and Conclusions:The prevalence of alcohol use disorders in all wards was 20%. Half of these patients were alcohol dependent, a quarter were diagnosed as alcohol abusers, and a quarter had an alcohol‐related problem that was not identified during the stay. Alcohol use disorders were more common in male inpatients (34% vs. 8% in female inpatients) and in certain age groups. One male subject in two and one female subject in five between 34 and 45 years had an alcohol‐related problem. Almost 25% of male inpatients studied between the ages of 16 and 20 years had an alcohol‐related problem, but only half had been diagnosed previously.Hospital care for alcohol‐related health problems was seriously inadequate. On average, 38% of patients diagnosed with an alcohol use disorder received relevant nonsomatic alcohol care, of which 13% were alcohol abusers and 50% were alcohol‐dependent patients.Significance:This exhaustive study demonstrates the degree of alcohol‐related morbidity among hospitalized patients, which is particularly high in men, in the Auvergne region of France. The study emphasizes the lack of diagnosis, particularly for the young, and the apparent deficiencies in the hospital management of these patients.
Mitochondrial Glutathione Replacement Restores Surfactant Synthesis and Secretion in Alveolar Epithelial Cells of Ethanol‐Fed Rats
Authors: Guidot David M. , Lou Brown Ann S. 
Published: May 2006

Background: Chronic alcohol abuse increases the incidence and severity of acute lung injury in critically ill patients. Previously we determined that ethanol ingestion in rats dramatically decreased alveolar epithelial cellular levels of glutathione and surfactant synthesis and secretion in vitro. Previous studies in alcoholic liver disease suggest that mitochondrial glutathione levels, and not cellular levels per se, are involved in the pathogenesis of ethanol‐mediated hepatotoxicity. Therefore, we hypothesized that alveolar epithelial mitochondrial glutathione depletion mediates the observed defects in surfactant synthesis and secretion in ethanol‐fed rats.Methods: Male Sprague‐Dawley rats were fed the Lieber‐DeCarli liquid diet with or without ethanol (36% of total calories) for 6 weeks. In some experiments, ethanol‐fed rats were then switched to the control diet for 1 week, with or without glutathione supplementation with either N‐acetylcysteine (NAC) or procysteine (PRO). Alveolar epithelial type II cells were then isolated and glutathione levels (cytosolic and mitochondrial) and surfactant production (synthesis and secretion) were determined.Results: Ethanol ingestion decreased (p < 0.05) mitochondrial and cytosolic levels of glutathione, and surfactant synthesis and secretion in isolated type II cells when compared to cells from control‐fed rats. NAC treatment restored (p < 0.05) cytosolic but not mitochondrial glutathione levels (p > 0.05), and had no effect (p > 0.05) on surfactant synthesis and secretion in type II cells isolated from ethanol‐fed rats. In contrast, PRO treatment restored (p < 0.05) cytosolic and mitochondrial glutathione levels, and normalized (p < 0.05) surfactant synthesis and secretion in type II cells isolated from ethanol‐fed rats.Conclusions: These results suggest that mitochondrial, and not simply cytosolic, replacement of glutathione is necessary to improve surfactant function in critically ill patients with a history of alcohol abuse.
Prenatal Alcohol Exposure and Depressive Features in Children
Authors: O'Connor Mary J. , Kasari Connie 
Published: May 2006

Background: This study examined the association between prenatal alcohol exposure and self‐report of depressive symptoms in 5‐ to 6‐year‐old children. Higher levels of prenatal alcohol exposure were hypothesized to be associated with endorsement of a greater number of depressive symptoms in children. It was also hypothesized that maternal depression, although associated with drinking behavior, would contribute independently to outcome. Finally, the mother's behavior toward the child, as well as current drinking practices, were postulated to mediate the relationship between prenatal alcohol exposure and child depressive symptoms.Methods: Participants were 41 mother‐child dyads who had been followed longitudinally since the children were 1 year of age. Self‐report questionnaires for maternal and child depression were used.Results: Results revealed that prenatal alcohol exposure, maternal depression, and child gender seemed to be highly associated with child depressive symptoms. Girls who had higher levels of prenatal alcohol exposure and whose mothers acknowledged higher levels of depression endorsed the highest number of depressive symptoms. Neither the mother's behavior in interaction with the child nor her current level of alcohol consumption mediated the relationship.Conclusions: The importance of considering prenatal alcohol exposure as a risk variable in the prediction of childhood‐onset depression and the possible neurological mechanisms underlying depression in children with alcohol exposure in utero are discussed.
5‐HT Transporter Sites and 5‐HT1A and 5‐HT3 Receptors in Fawn‐Hooded Rats: A Quantitative Autoradiography Study
Authors: Chen Feng , Lawrence Andrew J. 
Published: May 2006

Background: The neuroanatomical profiles of 5‐HT1A receptors, 5‐HT3 receptors, and 5‐HT transporters (5‐HTT) in the brain of the Fawn‐Hooded (FH) rat, particularly mesocorticolimbic regions, are not fully elucidated.Methods: By means of in vitro quantitative autoradiography, we used [3H]citalopram, [3H]8‐OH‐DPAT, and [H]GR65630 to label 5‐HTT, 5‐HT1A receptors, and 5‐HT3 receptors in the brain of alcohol‐naïve FH rats, Wistar‐Kyoto (WKY) rats, and FH rats given free access to 5% ethanol and/or after 24 to 48 hr withdrawal.Results and Conclusions: In alcohol‐naïve rats, FH rats displayed significantly higher (p < 0.05) densities of [3H]citalopram binding in the nucleus accumbens (+30%), lateral septum (+37%), ventral pallidum (+21%), and ventral tegmental area (+24%), as well as an increased binding of [3H]8‐OH‐DPAT to 5‐HT1A receptors in the frontal and parietal cortex (+33%), occipital and temporal cortex (+25%), and hippocampal CA3 region (+31%), compared with WKY rats, whereas both strains exhibited comparable [3H]GR65630 binding to 5‐HT, receptors. Compared with control FH (naïve) rats, chronic ethanol consumption significantly decreased (p < 0.05) [3H]8‐OH‐DPAT binding in the frontal and parietal cortex (‐15%) but significantly increased binding (p < 0.05) in the entorhinal cortex (+25%), retrosplenial granular cortex (+20%), and hippocampal CA1 (+14%) and CA3 regions (+18%). Moreover, ethanol withdrawal induced the same extent of increased [3H]8‐OH‐DPAT binding in the entorhinal and retrosplenial cortex as seen in FH (chronic) rats. In contrast, [3H]8‐OH‐DPAT binding in the hippocampal CA1 and CA3 regions was decreased by ‐9% and ‐20% from the level of chronic ethanol‐treated FH rat (p < 0.05) and returned to the control level seen in FH (naïve) rats.Significance:The elevated 5‐HT transporters and 5‐HT1A receptors in the mesocorticolimbic areas in FH rats may reflect a potential innate altered transmission at serotonergic synapses, which possibly may affect the high intake of alcohol in FH rats. The region‐specific alterations of 5‐HT1A receptors in FH rat brain after ethanol challenges suggest that 5‐HT1A receptors are sensitive to ethanol challenges, whereas 5‐HTT are apparently insensitive.
Short‐Term Acetaldehyde Exposure Depresses Ventricular Myocyte Contraction: Role of Cytochrome P450 Oxidase, Xanthine Oxidase, and Lipid Peroxidation
Authors: Aberle Nicholas S. , Ren Jun 
Published: May 2006

Background: Chronic alcoholism leads to the development of alcoholic cardiomyopathy, manifested as ventricular dilation and impaired ventricular contractility. However, the specific toxic mechanism responsible for alcoholic cardiomyopathy remains unclear. One major candidate toxin is the first metabolic product of ethanol, acetaldehyde (ACA). This study was designed to examine the role of cytochrome P450 oxidase 2E1 (CYP 2E1), xanthine oxidase, and lipid peroxidation in the short‐term ACA exposure‐induced mechanical defects in adult rat ventricular myocytes.Methods: Mechanical and intracellular Ca2+ properties were evaluated by an IonOptix SoftEdge® system. Lipid peroxidation was assessed with malondialdehyde levels by using high‐performance liquid chromatography.Results: Short‐term (4‐ to 6‐hr) culture of myocytes with ACA (1–100 μM) in sealed containers with silicone septum depressed cell‐shortening amplitude, maximal velocity of shortening/relengthening, and prolonged duration of relengthening, as well as intracellular Ca2+ clearing without any effect on the duration of shortening and electrically stimulated an intracellular Ca2+ increase. It is interesting to note that the ACA‐induced effects on myocyte mechanical properties were abolished with co‐treatment of the lipid peroxidation inhibitor butylated hydroxytoluene (20 μM), the CYP 2E1 inhibitor diallyl sulfide (100 μM), and the xanthine oxidase inhibitor allopurinol (100 μM). Short‐term incubation of ACA with the myocytes also produced a significant increase of the lipid peroxidation end product malondialdehyde, which may be prevented by butylated hydroxytoluene.Conclusions: Collectively, these data provided evidence that ACA depressed cardiomyocyte mechanical function at micromolar levels, possibly through mechanisms related to CYP oxidase, xanthine oxidase, and lipid peroxidation.
Cross‐Sensitization Between the Locomotor Stimulant Effects of Ethanol and Those of Morphine and Cocaine in Mice
Authors: Lessov Christina N. , Phillips Tamara J. 
Published: May 2006

Background: Drugs of abuse may share some common mechanisms of action. We examined this idea by determining whether cross‐sensitization would occur between the locomotor stimulant effects of ethanol (EtOH) and those of morphine and cocaine.Methods: Genetically heterogeneous adult female mice were repeatedly treated with 2.5 g/kg EtOH, then challenged 24 hr later with one of four doses of morphine or cocaine (0, 5, 10, or 20 mg/kg for both drugs). Under the reciprocal conditions, mice were repeatedly injected with cocaine or morphine (10 or 20 mg/kg), then challenged 24 hr later with 2.0 g/kg EtOH. In all cases, locomotor responses were compared to those of repeatedly saline‐treated control groups.Results: Behavioral sensitization was seen to the stimulant effects of EtOH, and to the effects of the higher, 20 mg/kg dose of both morphine and cocaine. EtOH‐sensitized mice did not show cross‐sensitization to morphine or cocaine. However, both single and multiple morphine pre‐exposures induced enhanced activation to an EtOH challenge. Mice repeatedly injected with 10 or 20 mg/kg cocaine also exhibited increased sensitivity to the stimulant effects of EtOH.Conclusions: There is some overlap in the neural mechanisms underlying behavioral sensitization to the locomotor stimulant effects of EtOH and those mediating sensitization to the locomotor stimulant effects of morphine and cocaine. Differences seen under reciprocal treatments may be associated with conditioning factors, or reflect differences in the neurobiological specificity of the effects of these drugs.
Fragmentary Blackouts: Their Etiology and Effect on Alcohol Expectancies
Authors: Hartzler Bryan , Fromme Kim 
Published: May 2006

Background: Fragmentary blackouts, or memory loss for intoxicated events that may be later recalled with the provision of cues, are common sequelae of heavy drinking, yet understanding of their characteristics, correlates, and consequences is limited. Consequently, this alcohol‐administration study addressed questions regarding the etiology of fragmentary blackouts and their effect on alcohol outcome expectancies.Methods: A placebo‐controlled design addressed the etiology of fragmentary blackouts through assessment of memory formation before and after alcohol consumption. The effect of fragmentary blackouts on prospective beliefs about alcohol was assessed by way of a self‐report outcome expectancy questionnaire and a measure of response latency for alcohol concepts presented after beverage consumption.Results: Although participants performed similarly on memory indices before consuming beverages, those who reported past fragmentary blackouts and consumed alcohol displayed marked difficulty with recall of a narrative when this was attempted both during intoxication and after detoxification, as well as with a source memory task presented during intoxication. Those reporting fragmentary blackouts also endorsed stronger outcome expectancies for a range of alcohol effects and exhibited greater accessibility for positive alcohol concepts presented after beverage administration. Further, source recall contributed significantly to the episodic recall both during intoxication and after detoxification, as well as to positive outcome expectancies of those receiving alcohol.Conclusions: Findings suggest that fragmentary blackouts result from poor retrieval and that individual differences in retrieval emerge after alcohol is consumed. Further, one's recall of source aspects of material—its time and social context—is an important determinant of recall of stimuli and events encountered during intoxication, as well as of prospective expectations for positive alcohol effects. The collective findings expand our understanding of this complex yet common neuropsychological consequence of heavy drinking.