bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self‐Reported Subjective Perception of Intoxication Reflects Family History of Alcoholism When Breath Alcohol Levels Are Constant
Authors: Morzorati S. L. , Ramchandani V. A. , Flury L. , Li T.‐K. , O'Connor S. 
Published: April 2006

Background The premise of this study is that the increased familial risk for alcoholism is associated with genetic determinants of the response to alcohol, characterized by sensitivity and adaptation. Following a single administration, sensitivity is the initial response to alcohol, expressed as the change in dependent measures from baseline. Adaptation of dependent measures within a single exposure to alcohol can be expressed as acute tolerance (recovery of dependent measures toward baseline values) or sensitization (movement of dependent measure further away from baseline values). This study tested the hypothesis that family history‐positive (FHP) subjects are more sensitive and more adaptive to alcohol compared with family history‐negative (FHN) subjects.Methods The initial response and development of adaptation to alcohol were assessed by using self‐reported subjective perceptions during a breath alcohol concentration (BrAC) clamp of 60 mg%. The Biphasic Alcohol Effects Scale, the Sensation Scale and a visual analog scale of intoxication were acquired at baseline, after the BrAC clamp was established, and after maintenance of the clamp for 105 min.Results FHP subjects were more sensitive to alcohol compared with FHNs, as evidenced by greater changes in feelings of intoxication when the BrAC clamp was initially achieved. While the clamp was maintained, the FHP subjects adapted to the effects of alcohol and their perceptions of intoxication became indistinguishable from those of the FHN subjects. The FHP subjects had developed acute tolerance to alcohol, whereas the FHN subjects did not. Other self‐reported perceptions of alcohol's effects did not distinguish between the groups.Conclusions A differential family history of alcoholism was reflected in self‐reported subjective perceptions of intoxication when the brain's exposure to a specified concentration of alcohol was held constant (BrAC of 60 mg%). FHP subjects reported greater intoxication after alcohol and subsequently developed acute tolerance to alcohol compared with FHN subjects.
Administration of Low Doses of MK‐801 During Ethanol Withdrawal in the Developing Rat Pup Attenuates Alcohol's Teratogenic Effects
Authors: Thomas J. D. , Fleming S. L. , Riley E. P. 
Published: April 2006

Background Alcohol exposure during development can produce severe and long‐lasting central nervous system damage and consequent behavioral alterations. Recent evidence suggests that NMDA receptor‐mediated excitotoxicity during periods of withdrawal may contribute to this damage. We have demonstrated that blocking the NMDA receptor with MK‐801 during alcohol withdrawal can attenuate ethanol's adverse effects on behavioral development in the rat. This study examined the dose dependency of MK‐801's ability to mitigate ethanol's teratogenic effects.Methods Neonatal rat pups were exposed to 6.0 g/kg of ethanol in a binge‐like manner on postnatal day (PD) 6, a period of brain development equivalent to a portion of the human third trimester. Alcohol administration was accomplished with an artificial rearing procedure. Twenty‐one hours after ethanol treatment, pups were injected intraperitoneally with one of four doses of MK‐801 (0.05, 0.1, 0.5, or 1.0 mg/kg) or saline vehicle. An artificially reared control and a normally reared control group were included. On PD 18–19, activity level was monitored, and on PD 40–42, serial spatial discrimination reversal learning was assessed.Results Alcohol exposure on PD 6 produced significant increases in activity level and deficits in reversal learning. These alcohol‐induced behavioral alterations were significantly attenuated in subjects treated with one of the three lower doses (0.05–0.5 mg/kg) of MK‐801 during withdrawal. The performance of ethanol‐exposed subjects treated with the high dose of MK‐801 (1.0 mg/kg) did not differ from that of the Ethanol Only group.Conclusions These data suggest that alterations in NMDA receptor activation during alcohol withdrawal contribute to the neuropathology and consequent behavioral alterations associated with developmental alcohol exposure. These data have important implications for pregnant women and newborns undergoing ethanol withdrawal.
Alcohol Dependence Symptoms and Alcohol Dehydrogenase 2 Polymorphism: Israeli Ashkenazis, Sephardics, and Recent Russian Immigrants
Authors: Hasin Deborah , Aharonovich Efrat , Liu Xinhua , Mamman Ziona , Matseoane Karen , Carr Lucinda G. , Li Ting‐Kai 
Published: April 2006

Background Jews have lower rates of alcohol‐related problems than other Caucasians. The ADH2*2 allele of the alcohol dehydrogenase 2 (ADH2) gene protects against alcoholism in Asians and is found in approximately 20% of Jews. We studied the relationship of ADH2*2 to DSM‐IV dependence severity in a random community sample of Israeli Ashkenazis, recent Russian immigrants (also Ashkenazis), and Sephardics.Methods Subjects participated in a structured interview that included highly reliable questions on DSM‐IV alcohol dependence symptoms. ADH2 genotype was determined for 68 subjects.Results Recent Russian immigrants had more past and lifetime DSM‐IV dependence symptoms. Sephardics had a higher prevalence of ADH2*2 than Ashkenazis. Controlling for group and other potentially confounding factors, ADH2*2 was associated with a lower lifetime DSM‐IV alcohol dependence severity, although this differed somewhat within groups.Conclusions ADH2*2 protects against dependence severity in Jewish samples. Future work in larger samples should address genetic and environmental factors that affect the relationship of ADH2*2 to alcohol consumption and dependence.
Association Study of Alcoholism Subtypes with a Functional Promoter Polymorphism in the Serotonin Transporter Protein Gene
Authors: Kranzler Henry , Lappalainen Jaakko , Nellissery Maggie , Gelernter Joel 
Published: April 2006

Background Association studies of a reportedly functional polymorphism in the promoter region (5′‐HTTLPR) of the gene encoding the serotonin transporter protein (genetic locus SLC6A4) in alcoholics have yielded conflicting results. The most frequently observed alleles of the 5′‐HTTLPR polymorphism are the short and long variants; the short variant is associated with lower transcriptional activity of the SLC6A4 gene than is the long variant. To reduce the heterogeneity that may confound association studies of alcohol dependence, we examined the association of 5′‐HTTLPR alleles with three dichotomous typologies of alcoholism based on sex, comorbid drug dependence, or age of onset of alcohol dependence.Methods A sample of 471 alcohol‐dependent subjects [363 European Americans (EAs) and 108 African Americans (AAs)] and 235 control subjects (192 EAs and 43 AAs) were included in the analyses. Alcohol dependence diagnoses were made using a structured interview. DNA isolated from whole blood was PCR‐amplified, and genotypes were assigned on the basis of agarose gel size fractionation.Results Although allele frequencies differed significantly by population, there was no evidence of differences by diagnosis or as a function of any of the three subtypes.Conclusions Variable findings in the literature in relation to the association of 5′‐HTTLPR alleles to alcohol dependence seem to be due to factors other than the composition of study samples in terms of univariate typologies based on sex, comorbid drug dependence, or age of onset of alcohol dependence.
The Influence of Trait Anger on the Alcohol‐Aggression Relation in Men and Women
Authors: Giancola Peter R. 
Published: April 2006

Background The purpose of this study was to investigate the influence of trait anger on alcohol‐related aggression in men and women.Methods Subjects were 204 healthy social drinkers (111 men and 93 women) between 21 and 35 years of age. Trait anger was measured using the Spielberger Trait Anger Scale. After 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 Of all of the variables, provocation was the strongest elicitor of aggression. Overall, anger was positively related to aggression for all subjects. However, the central finding of this study was that alcohol was more likely to increase aggression for persons, particularly men, with higher, as opposed to lower, levels of trait anger.Conclusions The results show that alcohol consumption does not increase aggression for all persons and in all situations. A continuing goal for future research in this area is to identify which individual difference and which contextual factors are most important in determining who will and who will not behave in an aggressive manner when intoxicated.
Longitudinal Brain Metabolic Characterization of Chronic Alcoholics With Proton Magnetic Resonance Spectroscopy
Authors: Parks Mitchell H. , Dawant Benoit M. , Riddle William R. , Hartmann Steven L. , Dietrich Mary S. , Nickel Mark K. , Price Ronald R. , Martin Peter R. 
Published: April 2006

BackgroundProton magnetic resonance spectroscopy may elucidate the molecular underpinnings of alcoholism‐associated brain shrinkage and the progression of alcohol dependence.MethodsUsing proton magnetic resonance spectroscopy, we determined absolute concentrations ofN‐acetylaspartate (NAA), creatine/phosphocreatine (Cr), and choline (Cho)‐containing compounds andmyo‐inositol (mI) in the anterior superior cerebellar vermis and frontal lobe white matter in 31 alcoholics and 12 normal controls. All patients were examined within 3 to 5 days of their last drink. Patients who did not relapse were again studied after 3 weeks and 3 months of abstinence by using an on‐line repositioning technique that allows reliable localization of volumes of interest (VOIs).ResultsAt 3 to 5 days after the last drink, frontal white matter metabolite concentrations were not significantly different from those of normal controls, whereas brain tissue in the VOI was reduced. Cerebellar [NAA] and [Cho] and brain and cerebellar volumes were decreased, but [Cr], [mI], and VOI brain tissue volume were not significantly different. Eight patients relapsed before 3 weeks (ER), 12 relapsed between 3 weeks and 3 months (LR), and 11 did not relapse (NR) during 3 months. Cerebellar [NAA] was reduced only in ER patients, despite the fact that ER patients drank for significantly fewer years and earlier in life than LR or NR patients. After 3 months, in the 11 continuously abstinent patients, cerebellar [NAA] and brain and cerebellar volumes increased; cerebellar [Cho], [Cr], and [mI] and VOI brain tissue did not change significantly.ConclusionsDecreased [NAA] and [Cho] in cerebellar vermis indicate a unique sensitivity to alcohol‐induced brain injury. Cerebellar [NAA] increased with abstinence, but reduced [Cho] persisted beyond 3 months. Further studies are needed to determine whether low cerebellar [NAA] is a risk factor for, or consequence of, malignant, early‐onset alcoholism.
Ethanol‐Induced Modulation of Inducible Nitric‐Oxide Synthase Activity in Human A172 Astrocytoma Cells
Authors: Davis Randall L. , Dertien Janet , Syapin Peter J. 
Published: April 2006

Background Glial cells are critical in the functioning of the central nervous system (CNS), including responsiveness to injury and immunocompetence. The immune and inflammatory response involves the inducible form of nitric‐oxide synthase (iNOS), and subsequent nitric oxide (NO) production. Previously, we have demonstrated that ethanol inhibits cytokine‐induced iNOS expression and activity in rat glial cells. Evidence of ethanol‐induced effects on iNOS in human glial cells is nonexistent. Herein, the conditions necessary for significant iNOS induction in human A172 astrocytoma cells have been characterized, and subsequently, the effects of ethanol on iNOS expression have been investigated.Methods A172 cells were analyzed immunohistochemically for the astrocyte markers, glial fibrillary acidic protein (GFAP) and S‐100β. The ability of A172 cells to express iNOS was assessed by stimulating cells with interferon‐γ (IFNγ), tumor necrosis factor‐α (TNFα), interleukin‐1β (IL‐1β), bacterial lipopolysaccharide (LPS), L‐arginine, and tetrahydrobiopterin (BH4) in various combinations. Following stimulation, iNOS induction was monitored via measurement of nitrite production and in vitro iNOS enzyme activity. Time‐course (6–24 hr) studies assessed the effects of ethanol (50–200 mM) on iNOS induction.Results Immunohistochemistry analysis confirmed that A172 cells were phenotypically, astrocytic. Induction of nitrite production by a cytomix [IFNγ (100 ng/ml) + TNFα (30 ng/ml) + IL‐1β (5 ng/ml)] was differentially enhanced by exposure to supplemental factors including LPS, L‐arginine, and BH4. Nitrite production was greatest over the initial 24 hr of stimulation with iNOS enzyme activity peaking at 12 hr. Acute (6–24 hr) exposure of activated cells to 50 mM ethanol enhanced iNOS activity recovered from the cytosol, whereas 200 mM ethanol decreased it. Ethanol had no direct effect on the catalytic activity of the enzyme.Conclusions The present study is the first published report of ethanol‐induced modulation of iNOS expression in human glial cells. The data suggest that ethanol is influencing iNOS enzyme levels most profoundly. Altered astrocyte function may be a point of ethanol‐induced perturbation in CNS immune function. These findings should lend insight into the role of ethanol on human CNS immunity and brain injury.
Increase of Rat Alcohol Drinking Behavior Depends on the Age of Drinking Onset
Authors: Yoshimoto Kanji , Hori Masafumi , Sorimachi Yoshihide , Watanabe Tetsushi , Yano Tadashi , Yasuhara Masahiro 
Published: April 2006

Background Although alcohol drinking onset in younger people is associated with an increased risk of alcohol‐related injuries, other factors, such as habituation and susceptibility to alcohol, in the process of aging have not been adequately examined in animal models. In the present study, we determined whether age of drinking onset affected alcohol drinking behavior and led to alcohol tolerance in experimental animals, and extrapolated some of the findings to human alcohol drinking patterns.Methods In the first experiment, 18 rats that were naive to alcohol were tested at the age of 1, 4, and 10 months with 4 hr of access to 10% (v/v) alcohol. After the time access tests, these animals (1, 4, and 10 months of age) were housed individually and given free access to 10% alcohol solution and tap water. At 3 and 6 months later, all rats that had experienced alcohol drinking were studied for the voluntary consumption of the alcohol solution, alcohol preference, under the two‐bottle method in a second experiment.Results In the 4‐hr alcohol‐access test, alcohol intake (g/kg/hr) was significantly increased at 0.5 and 1 hr in 1‐ and 4‐month‐old naive rats compared with 10‐month‐old naive rats. The daily alcohol intake (g/kg/day) of rats with drinking onset at 1 month of age was significantly increased at 3 and 6 months after the voluntary alcohol consumption. The daily alcohol intake in the rats with drinking onset at 4 months of age was significantly increased at 6 months only. However, the daily alcohol intake did not change in the rats with drinking onset at 10 months of age through the alcohol preference test.Conclusions Alcohol drinking behavior in experimental animals depends on the age of alcohol drinking onset.
Dopamine D2 Receptor Binding, Drd2 Expression and the Number of Dopamine Neurons in the BXD Recombinant Inbred Series: Genetic Relationships to Alcohol and Other Drug Associated Phenotypes
Authors: Hitzemann Robert , Hitzemann Barbara , Rivera Seth , Gatley John , Thanos Peter , Siming Shou Lu Lu , Williams Robert W. 
Published: April 2006

Background: It has not been established to what extent the natural variation in dopamine systems contribute to the variation in ethanol response. The current study addresses this issue by measuring D2 dopamine (DA) receptor binding, the expression of Drd2, the number of midbrain DA neurons in the BXD recombinant inbred (RI) series and then compares these strain means with those previously reported for a variety of ethanol and other drug‐related phenotypes.Methods: Data were collected for 21 to 23 of the BXD RI strains and the parental strains. D2 DA receptor autoradiography was performed using 125I‐epidepride as the ligand [Kanes S, Dains K, Cipp L, Gatley J, Hitzemann B, Rasmussen E, Sanderson S, Silverman S, Hitzemann R (1996) Mapping the genes for haloperidol‐induced catalepsy. J Pharmacol Exp Ther 277:1016–1025]. Drd2 expression was measured using the Affymetrix oligoarray system. Immunocytochemical techniques were used to determine the number of midbrain DA neurons [Hitzemann B, Dains K, Hitzemann R (1994) Further studies on the relationship between dopamine cell density and haloperidol response. J Pharmacol Exp Ther 271:969–976].Results and Conclusions: The range of difference in receptor binding for the RI strains was approximately 2‐fold in all regions examined, the core, the shell of the nucleus accumbens (NAc) and the dorsomedial caudate‐putamen (CPu); heritability in all regions was moderate—(h 2∼0.35). Drd2 expression in forebrain samples from the RI and parental strains ranged 1.5‐ to 2‐fold and h2 was moderate—0.47. Variation in the number of tyrosine hydroxylase (TH) positive neurons was moderate, 41% and 26% and h2 was low—0.19 and 0.15 for the ventral tegmental area (VTA) and substantia nigra compacta (SNc), respectively. Significant correlations were found between D2 DA receptor binding and the low dose (1.33 g/kg) ethanol stimulant response. (p < 0.002) and between Drd2 expression and conditioned place preference (CPP) (p < 0.0005). No significant correlations were detected between ethanol preference and either receptor binding or Drd2 expression; however, a significant correlation was found between preference and Ncam expression. Ncam is approximately 0.2 Mb from Drd2. Overall, the data suggest ethanol preference and CPP are associated with the expression of Drd2 or closely linked genetic loci.
High– and Low–Alcohol‐Preferring Mice Show Differences in Conditioned Taste Aversion to Alcohol
Authors: Chester Julia A. , Lumeng Lawrence , Li Ting‐Kai , Grahame Nicholas J. 
Published: April 2006

Background: Genetic differences in sensitivity to the aversive effects of alcohol may contribute to alcohol drinking behavior. The present study examined the development of conditioned taste aversion (CTA) to various doses of alcohol in two pairs of mouse lines selectively bred for high (HAP) and low (LAP) alcohol preference.Methods: Alcohol‐naïve, male and female HAP and LAP mice from both replicate 1 (HAP n= 29; LAP n= 28) and replicate 2 (HAP n= 34; LAP n= 35) were adapted to a 2‐hr per day water restriction regimen. During five conditioning trials at 48 hr intervals, mice received an intraperitoneal injection of saline or 2 g/kg or 4 g/kg alcohol immediately following 1 hr of access to a 0.20 M NaCl solution.Results: LAP mice of both replicates showed a significantly greater magnitude of CTA to both 2 g/kg and 4 g/kg alcohol compared with HAP mice of both replicates. There were no line differences in consumption of the NaCl solution in the saline control groups.Conclusions: These data suggest that mice selectively bred for low alcohol preference are more sensitive to the development of alcohol CTA than mice selectively bred for high alcohol preference. The present findings indicate that common genes mediate both alcohol preference and the aversive effects of alcohol as measured in the CTA paradigm.
Acutely Administered Ethanol Participates in Testosterone Synthesis and Increases Testosterone in Rat Brain
Authors: Alomary Ahmed A. , Vallée Monique , O'Dell Laura E. , Koob George F. , Purdy Robert H. , Fitzgerald Robert L. 
Published: April 2006

Background: The interaction of alcohol and testosterone has long been of interest, mainly due to the effect of alcohol on aggression and sexual behavior. To date, there have been very few, if any, studies examining the effect of acute alcohol administration on testosterone concentrations in the brain. The administration of 1,1‐dideuteroethanol ([1,1‐2H2]ethanol) provided the opportunity to trace the deuterium label into newly synthesized deuterotestosterone in brain samples to determine whether ethanol oxidation was directly linked to testosterone synthesis.Methods: Unoperated and adrenalectomized‐gonadectomized (ADX/GDX) rats were given either ethanol or [1,1‐2H2]ethanol in a single intraperitoneal dose of 2 g/kg body weight. We used gas chromatography/mass spectrometry to accurately determine both the amount of steroids present and the degree of deuterium incorporation into specific steroids isolated from brain samples.Results: Thirty minutes after alcohol administration, the level of total testosterone increased 4‐fold in the frontal cortex and 3‐fold in the plasma of unoperated male Wistar rats. The relative increase in the abundance of monodeuterated testosterone 30 min after [1,1‐2H2]ethanol administration was significant (p < 0.05) in both brain and plasma. ADX/GDX animals treated with alcohol had testosterone concentrations that were 5% of those found in unoperated animals dosed with ethanol.Conclusions: Acutely administered ethanol increased brain concentrations of testosterone 4‐fold in male Wistar rats. ADX/GDX surgery reduced brain concentrations of testosterone in response to alcohol by 95%. The deuterium labeling of testosterone after [1,1‐2H2]ethanol showed that ethanol oxidation is directly linked to testosterone biosynthesis and that the deuterium‐labeled testosterone is present in the central nervous system. These results demonstrate that peripherally administered ethanol directly contributes to the concentrations of testosterone in the central nervous system and that the testosterone found in brain samples is primarily synthesized in the periphery. These findings may be important for understanding the behavioral changes associated with acute alcohol consumption.