bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Gender and Estrous Cycle on the Pharmacokinetics of Ethanol in the Rat Brain
Authors: Robinson Donita L. , Brunner Lane J. , Gonzales Rueben A. 
Published: April 2006

Background: Aspects of ethanol pharmacokinetics in the blood, such as elimination, are known to vary by gender in the rat. Ethanol concentrations reaching the brain, which are relevant in affecting behavior, have not been measured rigorously by gender. This study used quantitative microdialysis to measure ethanol pharmacokinetics in the nucleus accumbens after a moderate dose of ethanol, comparing males with females and females across the estrous cycle.Methods: We administered 1 g/kg ethanol intravenously or intragastrically to male and female rats. We measured ethanol concentrations in the nucleus accumbens by use of microdialysis with in vivo probe calibration and compared them with concentrations in jugular venous blood.Results: After intravenous delivery, apparent ethanol elimination was approximately 15% faster in females than males from both brain and blood. After intragastric delivery, blood ethanol concentrations peaked faster in females than males by approximately 20 min, suggesting faster absorption or diffusion from the stomach. Likewise, accumbal ethanol concentrations peaked faster in females than males by approximately 25 min, indicating faster distribution to the brain. These pharmacokinetic parameters did not vary across the estrous cycle, nor were they influenced significantly by body water.Conclusions: This study provides the first quantitative measurement of ethanol concentrations and, thus, pharmacokinetics in the brain of awake rats. If ethanol distribution to the brain varies between genders, as these results suggest, then differences in the pharmacological response to ethanol can be expected, providing a rationale for studying the pharmacodynamics of ethanol in the brain of the self‐administering rat.
Antagonistic Effects of Dopaminergic Signaling and Ethanol on Protein Kinase A–Mediated Phosphorylation of DARPP‐32 and the NR1 Subunit of the NMDA Receptor
Authors: Edwards Scott , Simmons Diana L. , Galindo David G. , Doherty James M. , Scott Anne M. , Hughes Peter D. , Wilcox Richard E. 
Published: April 2006

Background: This article extends our initial investigation of the interactions between dopamine and glutamate receptor systems after acute exposure to ethanol. DARPP‐32 (dopamine and cyclic adenosine monophosphate–regulated phosphoprotein of approximate molecular weight 32 kDa) is an important regulator of protein phosphatase‐1 that in turn regulates a large number of effectors, including the NMDA receptor.Methods: We measured the protein kinase A (PKA)–mediated phosphorylation of DARPP‐32 and the NR1 subunit of the NMDA receptor. Initially, corpus striatum was assayed after intraperitoneal treatment of mice with the D1 agonist SKF82958, the D2 agonist and anticraving drug bromocriptine, or ethanol. In other experiments we blocked D1 receptors with the selective D1 antagonist SCH23390 or blocked D2 receptors with the selective D2 antagonist eticlopride. Finally, we examined combinations of some dopaminergic drugs with and without ethanol.Results: SKF82958 alone significantly increased PKA‐mediated phosphorylation of both DARPP‐32 and NR1. Bromocriptine alone had no effect on pDARPP‐32 or on pNR1. However, when D1 receptors were blocked, bromocriptine reduced the PKA‐mediated phosphorylation of both DARPP‐32 and NR1. Coincident treatment with bromocriptine and ethanol reversed both of these effects with D1 receptors blocked. The combination of eticlopride (D2 blocker) and SF82958 (D1 agonist) did not significantly alter either pDARPP‐32 or pNR1.Conclusions: These data demonstrate antagonistic effects of acute ethanol exposure on D1 signaling in vivo and the potential of acute in vivo challenge protocols to help fill gaps in the understanding of ethanol's effects on protein phosphorylation.
Automating Standard Alcohol Use Assessment Instruments Via Interactive Voice Response Technology
Authors: Mundt James C. , Bohn Michael J. , King Monica , Hartley Michael T. 
Published: April 2006

Background: Interactive voice response (IVR) technology integrates touch‐tone telephones with computer‐automated data processing. IVR offers a convenient, efficient method for remote collection of self‐report data.Methods: Twenty‐six subjects recruited from an outpatient alcohol treatment center completed IVR and paper/pencil versions of a demographic and drinking history questionnaire, Stages of Change Readiness and Treatment Eagerness Scale, Drinker Inventory of Consequences, Obsessive‐Compulsive Drinking Scale, Alcohol Dependence Scale, and two numerical rating scales of craving and desire to drink during the prior week. Administration of the instruments in both formats was repeated 1 week later. The order of administration method was counterbalanced between subjects and reversed across data collection sessions. Scale and subscale scores from both methods were correlated within sessions. Test‐retest correlations were also calculated for each method. A criterion of α= 0.01 was used to control type I statistical error.Results: Intermethod correlations within each session were significant for all of the instruments administered. Test‐retest correlations for both methods were also significant, except for the numerical ratings. Scores on the Alcohol Dependence Scale obtained via IVR were significantly lower than those collected by paper/pencil. Other differences between the data collection methods or across the sessions were inconsistent. The average IVR call length was 34 min and 23 sec. Paper/pencil forms required an average of 18 min and 38 sec to complete and an additional 10 min and 17 sec for data entry.Conclusions: IVR technology provides a convenient alternative to collecting self‐report measures of treatment outcomes. Both paper/pencil and IVR assessments provide highly convergent data and demonstrate good test‐retest reliability. Alcohol Dependence Scale score differences between methods highlight special considerations for IVR adaptation of existing paper/pencil instruments. Benefits of IVR include procedural standardization, automatic data scoring, direct electronic storage, and remote accessibility from multiple locations.
Response of Saccadic Eye Movements to Alcohol in African American and Non‐Hispanic White College Students
Authors: Blekher T. , Beard J. D. , O'Connor S. , Orr W. E. , Ramchandani V. A. , Miller K. , Yee R. D. , Li T‐K. 
Published: April 2006

Background: The primary goal of this study was to evaluate how race and sex interact with the effects of a moderate dose of alcohol on different ocular control subsystems in African American (AA) and non‐Hispanic white American (WA) college students.Methods: Horizontal visually guided (VG) saccades and antisaccades (AS) of 80 young adult, healthy, AA and WA college students were recorded with an infrared system. Subjects ingested 10 aliquots of ethanol at 3 min intervals, with the aggregate dose precalculated to yield a peak breath alcohol concentration (BrAC) of 80 mg%. Data from the measures performed at baseline and the ascending and descending limbs of the BrAC at ∼65 mg% were compared across race and sex by multivariate analysis of variance. A no‐alcohol control session, performed in 20 of the subjects, documented test‐retest reliability of the VG and AS measurements.Results: Both AA and WA groups demonstrated slowing of AS and VG saccades after alcohol administration, but there was no significant effect of 65 mg% alcohol on VG accuracy or AS errors. AS latency recovered toward baseline values, whereas the slowing of VG latency/velocity progressed, during alcohol exposure. There were significant differences between AA and WA groups in the time course of VG latency after alcohol but not in most other dependent measures. No significant effects for sex were observed in any of the saccade measures. The faster disappearance of alcohol in WA compared with AA was replicated, and some measures demonstrated a significant, albeit small, negative correlation between the alcohol disappearance rate and impairing effects of alcohol on saccades.Conclusions: Prolonged latencies and unchanged percentage of errors reflect a differential effect of alcohol on neural function in specific areas (parietal eye field, superior colliculus, and frontal eye areas). Race may interact with the effect of ethanol on saccadic eye movements in a college student population.
Ethanol, Acetaldehyde, Acetate, and Lactate Levels After Alcohol Intake in White Men and Women: Effect of 4‐Methylpyrazole
Authors: Sarkola Taisto , Iles Matthew R. , Kohlenberg‐Mueller Kathrin , Eriksson C. J. Peter 
Published: April 2006

Background: 4‐Methylpyrazole (4‐MP), a selective inhibitor of alcohol dehydrogenase (ADH), recently has been approved for clinical use in humans. The objective was to evaluate the use of 4‐MP in human alcohol research and to study the effect of 4‐MP on various parameters of alcohol metabolism during alcohol intoxication.Methods: 4‐MP (10–15 mg/kg orally) or placebo was given in double‐blind fashion to 22 premenopausal women, 12 of whom were using oral contraceptives, and 13 men followed by intake of alcohol (0.5 g/kg orally) or placebo.Results: A 30% to 40% decrease in the ethanol elimination rate was observed in the different groups during pretreatment with 4‐MP. The alcohol‐induced increase in plasma acetate was partially inhibited by 4‐MP. A significant positive correlation was observed between the effect of 4‐MP on the alcohol‐induced lactate and acetate elevations. The acetaldehyde was nondetectable (<1 μmol/liter) in the peripheral venous blood during alcohol intoxication in both women and men. During alcohol intoxication, a decrease in breath acetaldehyde was found with 4‐MP pretreatment in women but not in men.Conclusion: The alcohol‐induced elevation in blood acetate level is caused, in part, by ADH‐mediated ethanol oxidation. Although no evidence was found for measurable acetaldehyde levels in the peripheral venous blood during alcohol intoxication, the effect of 4‐MP on breath acetaldehyde in women supports the view that ADH‐mediated acetaldehyde elevations reflected in the airways, but too low to be detected in the peripheral venous blood, may occur in women during alcohol intoxication in the present experimental conditions.
The Alcohol Use Disorders Identification Test (AUDIT): A Review of Recent Research
Authors: Reinert Duane F. , Allen John P. 
Published: April 2006

Background: Efficient, inexpensive screening for early stage alcohol problems is important in health care settings. The Alcohol Use Disorders Identification Test (AUDIT) has been studied extensively to establish its value in this regard.Methods: A literature search that used EtOH as a database was conducted to identify studies published on the AUDIT through September 2001. Keywords used for the search were “Alcohol Use Disorders Identification Test” and “AUDIT.” All studies reporting psychometric properties of the measure were reviewed with particular attention being given to the period 1996 and later. A small number of additional references were located by noting their citation in other studies reviewed.Results: Although more research is needed on non‐English versions to establish their psychometric properties, at least in its English edition, the AUDIT demonstrates sensitivities and specificities comparable, and typically superior, to those of other self‐report screening measures. Test‐retest reliability and internal consistency are also quite favorable. For males, the AUDIT‐C, a shortened version of the AUDIT, appears approximately equal in validity to the full scale.Conclusions: Recent research continues to support use of the AUDIT as a means of screening for alcohol use disorders in health care settings in the United States.
Ethanol Decreases the Efficiency of Phosphorylation of Thymidine Kinase in a Human T‐Lymphocytic Cell Line
Authors: Prakash Om , Tang Zhen‐Ya , Zhou Peng , Peng Xiaochan , Kolls Jay , Shellito Judd E. , Nelson Steve 
Published: April 2006

Background: Thymidine kinase (TK) and thymidylate kinase (TMPK) are the two rate‐limiting enzymes in the cascade of activation of the anti‐human immunodeficiency virus (HIV) drug 3′‐azido‐3′‐deoxythymidine (AZT) to its active triphosphate form. We examined the effect of ethanol and a combination of ethanol and AZT on TK and TMPK activities in human Jurkat T cells.Methods: Jurkat T cells were exposed to 0.2 and 0.5% (v/v) ethanol concentrations alone or in combination with 5 or 10 μM AZT for 48 hr in growth medium. TK and TMPK activities were determined by measuring the conversion of [3H] substrates (thymidine or AZT for TK and thymidine monophosphate for TMPK) to their respective monophosphate or diphosphate forms. The effect of ethanol on the transcriptional activity of TK was determined by reverse transcription–polymerase chain reaction and on the growth of Jurkat cells by [3H]‐thymidine incorporation and cell‐cycle analysis.Results: Treatment of Jurkat cells with 0.2 and 0.5% ethanol concentrations resulted in 25 and 50% decreases (p≤ 0.05) in TK activity, respectively. No significant changes were observed in the TMPK activities. However, ethanol decreased the formation of thymidine diphosphate from thymidine in coupled TK/TMPK reactions, suggesting that decreases in TK activity could result in an overall decrease in the phosphorylation of AZT. The effect of ethanol on TK was independent of its transcript level. AZT in combination with ethanol decreased the inhibitory effect of ethanol on TK activity. However, it did not block the ethanol effect even at higher concentrations. Ethanol significantly decreased the proliferative capacity and cell cycle progression of the Jurkat cells.Conclusions: Our in vitro study in human Jurkat T cells indicates that at physiologically achievable concentrations in humans, ethanol can decrease TK activity through decreases in cell proliferation, and it suggests that ethanol ingestion in HIV‐1–infected individuals could compromise activation of AZT and related drugs through decreased TK activity.
Microdialysis of Dopamine in the Nucleus Accumbens of Alcohol‐Preferring (P) Rats During Anticipation and Operant Self‐Administration of Ethanol
Authors: Melendez Roberto I. , Rodd‐Henricks Zachary A. , Engleman Eric A. , Li Ting‐Kai , McBride William J. , Murphy James M. 
Published: April 2006

Background: The present study was designed to test directly whether a contextual stimulus for access to ethanol would acquire the ability to enhance locomotor activity and dopamine efflux in the nucleus accumbens (NAc) of alcohol‐preferring (P) rats. The study also explored the association between elevated locomotor activity and NAc dopamine efflux during operant self‐administration of ethanol.Methods: Adult female P rats were randomly assigned to operantly self‐administer either 15% (v/v) ethanol or 0.0125% (w/v) saccharin. Both groups were trained in a daily 30‐min two‐lever concurrent operant task (FR‐3) to orally self‐administer ethanol or saccharin, with water on the alternate lever. A third (control) group was trained to self‐administer water on both levers. All groups were also acclimated in the operant chambers to periods of habituation, anticipation, and postadministration.Results: Compared with controls, the ethanol group, but not the saccharin group, showed significant increases in locomotor activity as well as increased NAc dopamine efflux during the first 10 min of the anticipation period. During the first 10 min of the self‐administration period, locomotor activity was significantly increased in both the ethanol and saccharin groups compared with control values. The ethanol group, but not the saccharin group, showed significant increases in NAc dopamine efflux during the 20th and 30th min of the self‐administration period and during the first 10 min of the postadministration period.Conclusions: The findings suggest that acquisition of signal‐induced anticipation of self‐administered ethanol is associated with increases in locomotor activity and extracellular levels of dopamine in the NAc of P rats. Such associations may be important to the development and maintenance of ethanol‐seeking behaviors. The findings also indicate that operant self‐administration of ethanol is associated with increases in extracellular levels of dopamine in the NAc of P rats.
Ethanol Enhances Activation‐Induced Caspase‐3 Dependent Cell Death in T Lymphocytes
Authors: Kelkar Sujata , Dong Qing , Xiao Yinghua , Joshi‐Barve Swati , McClain Craig J. , Barve Shirish S. 
Published: April 2006

Background: Clinical and experimental studies have shown that an important deleterious consequence of excessive alcohol consumption is immunosuppression, specifically, a depletion in the mature CD4+ T‐cell population. A predominant mechanism involved in T‐cell depletion is activation‐induced cell death (AICD). Although it is well documented that ethanol intake can cause depletion of CD4+ T cells, the mechanism of how alcohol mediates its effects is unclear.Methods: The results were based on data from three separate experiments presented as mean ± standard deviation (SD). Jurkat CD4+ T cells and peripheral blood lymphocytes were treated with 25 mM of ethanol (12–18 hr), followed by stimulation with mitogens Conconavalin A (5 μg/ml) and Phytohemmaglutinin (1 μg/ml) or T‐cell receptor ligation (anti‐CD3 antibody (5 μg/ml)) for 6 hr, and then harvested for measurement. The apoptotic cell death markers measured include cell viability, Caspase‐3‐like activity, and DNA fragmentation.Results: We demonstrate that alcohol pretreatment enhances AICD of Jurkat CD4+ T cells and peripheral blood lymphocytes upon activation by CD3‐crosslinking or stimulation with Conconavalin A and Phytohemmaglutinin. Furthermore, we find that the ethanol‐mediated enhancement of T cells to apoptosis involves increased activation of Caspase‐3 and can be abrogated by treatment with a specific inhibitor of Caspase‐3.Conclusions: Our data indicate that ethanol can sensitize CD4+ T cells to enhanced stimulation‐induced Caspase‐3 activation and to subsequent AICD. This is, perhaps, an important mechanism in alcohol‐induced immunosuppression.
Corpus Callosum, Pons, and Cortical White Matter in Alcoholic Women
Authors: Pfefferbaum Adolf , Rosenbloom Margaret , Serventi Kathleen L. , Sullivan Edith V. 
Published: April 2006

Background:To measure the effect of alcohol abuse on white matter brain macrostructure in women with alcoholism and to determine whether observed abnormalities interact with age.Methods:Quantitative measures of corpus callosum area, cortical white matter volume, and pons volume were derived from magnetic resonance imaging scans obtained from 34 women with DSM‐III‐R alcoholism (aged 28‐64, mean 41 years) and 35 healthy women (aged 22‐65, mean 42 years). Transverse relaxation time of the pons was also obtained.Results:No significant group differences in any brain measures were observed. However, in alcoholics greater length of sobriety was associated with more cortical white matter, and higher lifetime levels of alcohol consumption were associated with smaller volumes and prolonged transverse relaxation time in the pons.Conclusions:Despite a lack of overall deficits in white matter macrostructural size in alcoholic women, certain white matter structures showed alcohol exposure vulnerability whereas others showed evidence of recovery with abstinence.
Ethanol‐Induced Translocation of Protein Kinase A Occurs in Two Phases: Control by Different Molecular Mechanisms
Authors: Dohrman Douglas P. , Chen Hui‐min , Gordon Adrienne S. , Diamond Ivan 
Published: April 2006

Background: Cyclic adenosine monophosphate (cAMP)‐dependent protein kinase A (PKA) regulates cellular functions. The specificity of PKA‐mediated phosphorylation is determined primarily by PKA localization to sub‐cellular sites. Chronic exposure to ethanol causes sustained translocation of the PKA catalytic subunit (C) from the Golgi to the nucleus in NG108‐15 cells. Here we find that this is preceded by a transient short‐term ethanol‐induced translocation of PKA C. Different molecular mechanisms appear to underlie early and late phases of ethanol‐induced translocation of PKA subunits.Methods: The time course and localization of PKA C and regulatory (RII) subunits was assessed by immunocytochemistry in NG108‐15 cells in the presence of ethanol, adenosine receptor (A2) blockade, and inhibitors of PKA activity and RNA and protein synthesis.Results: Ethanol induces an early phase (<30 min) of C translocation to the cytoplasm and nucleus. This requires cAMP via adenosine A2 receptor activation. C then returns to the Golgi area after 60 min. A second phase of C translocation occurs during continuing exposure to ethanol (>12 hr). Re‐accumulation of nuclear C no longer requires A2 or cAMP. RII also translocates to the nucleus during chronic treatment with ethanol. Both C and RII remain in the nucleus as long as ethanol is present. Unlike the early phase of ethanol induced translocation, the second phase of PKA subunit translocation requires protein and RNA synthesis.Conclusions: We identify two distinct phases of ethanol‐induced PKA translocation which appear to be regulated by different molecular mechanisms. The first requires A2 signaling and cAMP; the later phase requires RNA and protein synthesis. The two phases of ethanol‐induced PKA translocation observed in cell lines may contribute to changes in PKA signaling, cAMP‐dependent gene expression, and the initiation and maintenance of sustained drinking behavior in experimental animals.
The Effects of NMDA and GABAA Pharmacological Manipulations on Ethanol Sensitivity in Immature and Mature Animals
Authors: Silveri M. M. , Spear L. P. 
Published: April 2006

Background: Sensitivity to the hypnotic effects of ethanol dramatically increases with age (Silveri and Spears, 1998). Little is known regarding the neural mechanisms that might underlie this relative resistance of young animals to ethanol. The present study used a psychopharmacological approach to examine the influence of NMDA (N‐methyl‐D‐aspartate) and GABA (γ‐Aminobutyric acid) receptor systems in modulating age differences in ethanol responsiveness between young [postnatal day (P26)] and mature (P70) female and male Sprague‐Dawley rats.Method: Dose response curves were established for the effects of intraperitoneal (ip) administration of the NMDA antagonist (+)MK‐801 (0.75, 1.0, or 1.25 mg/kg), the GABAA agonist muscimol (0.75, 1.25, or 1.75 mg/kg), or saline on loss and regain of the righting reflex and trunk blood alcohol levels following 3.5 g/kg of ethanol.Results: (+)MK‐801 increased time to regain the righting reflex at both ages, maintaining the age‐related increase in ethanol sensitivity typically observed, although a gender effect also emerged at P70, with females being more sensitive than males to (+)MK‐801‐induced increases in duration of loss of the righting reflex. In contrast to the across‐age similarity in responsiveness to (+)MK‐801, P26 animals were considerably more sensitive to muscimol's enhancing effect on ethanol sedation than mature animals.Conclusion: Although modulation of either the NMDA or GABA system enhances the sedative effects of ethanol at both ages, stimulation of the GABAA receptor is a more effective means of prolonging ethanol sedation in immature than mature animals.