bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Ethanol Excitation of Dopaminergic Neurons of the Ventral Tegmental Area After Chronic Ethanol Treatment
Authors: Brodie Mark S. 
Published: April 2006

Background The mesolimbic dopamine pathway, which originates in the ventral tegmental area (VTA), is important for the rewarding effects of ethanol. Acute administration of ethanol has been shown to excite dopaminergic neurons of the VTA. Chronic ethanol treatment has been reported to alter the in vitro response of dopaminergic neurons to NMDA and dopamine. The present electrophysiological study tested the hypothesis that the effect of ethanol, γ‐aminobutyric acid (GABA), and NMDA on individual dopaminergic VTA (DA‐VTA) neurons from C57BL/6J mice would be changed by chronic treatment with ethanol.Methods C57BL/6J mice were injected intraperitoneally twice daily with either saline or ethanol in saline (3.5 g/kg) for at least 21 days. Extracellular single unit recordings of spontaneous action potentials were made from DA‐VTA neurons in brain slices from these mice. Ethanol (20–120 mM), GABA (50–500 μM), or NMDA (2–20 μM) was administered in the superfusate, and the resulting change in firing rate was measured.Results There was no significant difference in mean basal spontaneous firing rate of DA‐VTA neurons between saline‐treated and ethanol‐treated mice. The DA‐VTA neurons from ethanol‐treated mice were excited by ethanol more potently than those from saline‐treated mice. Dopaminergic VTA neurons from ethanol‐treated mice were inhibited less potently by GABA than those from saline‐treated mice. There was no difference in the potency of NMDA to excite DA‐VTA neurons from saline‐treated and ethanol‐treated mice.Conclusions Chronic treatment of C57BL/6J mice with ethanol injections sensitizes DA‐VTA neurons to ethanol excitation and also decreases the inhibitory potency of GABA. The increase in sensitivity to ethanol excitation of dopaminergic VTA neurons after chronic ethanol treatment may increase the reward value of ethanol. This sensitization to ethanol activation may be an important change in reward area neurons and may contribute to the development of alcoholism.
Laboratory Tests for Acute Alcohol Consumption: Results of the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence
Authors: Helander Anders , Eriksson C. J. Peter 
Published: April 2006

Background The WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence aimed partly to evaluate the overall performance and cross‐national validity of traditional and new biological markers of alcohol use and abuse. This article focused on the sensitivity and specificity of ethanol and methanol concentrations in plasma, and the 5‐hydroxytryptophol (5HTOL) to 5‐hydroxyindole‐3‐acetic acid (5HIAA) ratio in urine, as laboratory tests to identify acute alcohol consumption. Comparison was made with self‐reported drinking levels.Methods Subjects were recruited in Australia, Brazil, Canada, Finland, and Japan. They were interviewed thoroughly about their alcohol consumption habits, by using the standardized WHO/ISBRA Interview Schedule, and were classified into four categories: nondrinkers, light/moderate drinkers, heavy drinkers (≥210 g ethanol/week for men, and ≥140 g/week for women), or patients who were receiving treatment for alcohol dependence. Ethanol and methanol determinations in plasma were carried out by headspace gas chromatography. Urinary concentrations of 5HTOL and 5HIAA were determined by using gas chromatography‐mass spectrometry and high‐performance liquid chromatography, respectively.Results The baseline levels (in nondrinkers) for methanol and the 5HTOL/5HIAA ratio did not differ markedly between the five populations, except for a considerably higher, but probably artifactual, methanol level in the Finnish plasma samples. Moreover, there were no apparent age or sex differences. The urinary 5HTOL/5HIAA ratio was the most, and ethanol the least, sensitive indicator of recent alcohol consumption, and this was true for the different drinking categories as well as for the five study populations. The highest frequency of elevated test results was observed among those classified as heavy drinkers (e.g., 38% were positive for 5HTOL/5HIAA). However, elevated values also were obtained in nondrinkers and in drinking subjects who denied any intake of alcohol within 2 days before the interview and blood/urine sampling, which suggested a low accuracy of self‐reports of alcohol consumption in certain individuals.Conclusions The present investigation demonstrated that plasma ethanol and methanol and urinary 5HTOL/5HIAA provide useful exclusion markers for any study of biological parameters that are affected by previous acute ethanol intoxication. The major advantage of methanol and 5HTOL/5HIAA over ethanol is that they can detect recent alcohol consumption even several hours after the ethanol is no longer measurable. The results suggest that the cutoff limits to be used for these markers are not dependent on the country or population to be studied.
Platelet Adenylyl Cyclase Activity as a State or Trait Marker in Alcohol Dependence: Results of the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence
Authors: Hoffman Paula L. , Glanz Jason , Tabakoff Boris 
Published: April 2006

Background There has been considerable interest in identifying biochemical markers indicative of a genetic predisposition to alcohol dependence (“trait markers”), as well as biochemical markers of recent alcohol drinking (“state markers”). Platelet adenylyl cyclase activity has been suggested as a trait and/or as a state marker related to alcohol dependence. We have now measured platelet adenylyl cyclase activity in more than 1400 well‐characterized subjects, which allows us to investigate the influence of a broad range of factors on this activity.Methods Subjects were recruited as part of the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence and were interviewed by using the WHO/ISBRA Interview Schedule. Adenylyl cyclase activity (basal, cesium fluoride [CsF]‐, forskolin‐ and Gpp(NH)p‐stimulated activities) was measured in platelet samples that were obtained at the time of interview. Data were analyzed by multivariate regression analyses.Results The multivariate analyses revealed that recent abstinence from alcohol was associated with diminutions in platelet adenylyl cyclase activities. A positive family history of alcohol dependence was associated with higher levels of adenylyl cyclase activities, and there was a significant interaction between the effect of alcohol consumption in the past month and family history of alcohol dependence; that is, the influence of alcohol consumption depended on whether the individual had a positive family history. A history of marijuana abuse also was associated with higher levels of platelet adenylyl cyclase activities, and a history of major depression was associated with lower levels of forskolin‐ and CsF‐stimulated activities. Sex, race, and site of recruitment also affected some adenylyl cyclase activities, but there was no significant association of alcohol dependence or abuse with any of the platelet adenylyl cyclase activities.Discussion The large population and extensive characterization of subjects in this study provided an advantage over previous studies in which only the association of a few individual factors with adenylyl cyclase activity was investigated. The results demonstrate that although platelet adenylyl cyclase activity could be useful as a trait marker of alcohol dependence, its reliability in this regard is diminished by the influence of recent alcohol drinking and other variables. The associations between platelet adenylyl cyclase activities and marijuana abuse, as well as a history of depression, suggest that it may be worthwhile to study the genetic association of adenylyl cyclases (e.g., polymorphisms in the genes that code for particular adenylyl cyclase isoforms) with a predisposition to depression as well as to alcohol or marijuana abuse/dependence.
Differences in the Responses of the Pituitary β‐Endorphin and Cardiovascular System to Ethanol and Stress as a Function of Family History
Authors: Dai Xing , Thavundayil Joseph , Gianoulakis Christina 
Published: April 2006

Background Genetic and environmental factors, such as stress, are important for the initiation and maintenance of heavy drinking, whereas β‐endorphin may be important in controlling alcohol consumption. These studies investigated the response of pituitary β‐endorphin to stress and the effect of alcohol on the stress response in subjects at low (LR) and high (HR) risk of alcoholism, as determined from their family history.Methods Twenty LR and 20 HR subjects were exposed to stress 30 min after ingestion of either a placebo or an alcohol drink. Plasma β‐endorphin was measured before and for 4 hr after the drink. Changes in the concentration of plasma β‐endorphin after ingestion of the placebo or alcohol drink alone served as controls to compare the stress‐induced changes. Pulse and diastolic and systolic blood pressure were also measured.Results HR subjects presented higher baseline values of pulse and systolic blood pressure and lower plasma β‐endorphin than LR subjects. Stress induced a small increase in cardiovascular activity, whereas alcohol induced a stronger stimulation. Alcohol before stress did not prevent the stress‐induced increase in cardiovascular activity. Stress, but not alcohol, increased the plasma β‐endorphin concentration. LR subjects presented a higher stress‐induced increase in plasma β‐endorphin and a faster recovery than HR subjects. Alcohol before stress attenuated the stress‐induced increase in plasma β‐endorphin in both LR and HR subjects. This attenuation was stronger in LR subjects.Conclusions Thus, there are differences in the response of β‐endorphin to stress and the effect of ethanol on stress responses as a function of a family history of alcoholism.
An Evaluation of Relations Among Antisocial Behavior, Psychopathic Traits, and Alcohol Problems in Incarcerated Men
Authors: Reardon Maureen Lyons , Lang Alan R. , Patrick Christopher J. 
Published: April 2006

Background The association between antisocial behavior and alcohol problems is well established, but the role that psychopathic traits and other factors such as drinking patterns and motives and family history play in this relationship has not been subjected to much empirical scrutiny.Methods A large sample (n= 329) of male Federal Correctional Institution inmates participated in structured interviews designed to permit diagnosis of antisocial personality disorder and to assess facets of psychopathic personality as defined by the Hare Psychopathy Checklist–Revised. Prisoners also completed self‐report questionnaires that addressed alcohol use, drinking problems, motives for drinking, and paternal alcoholism history.Results Analyses revealed that the relation between antisocial behavior and alcohol problems was moderated by scores on the emotional detachment component of psychopathy, and that self‐descriptions of drinking for the purpose of coping with negative emotions mediated the positive relation between antisociality and self‐reported alcohol problems.Conclusions These findings highlight complexities in the link between antisociality and drinking problems and encourage consideration of distinct facets of psychopathy to enhance understanding of it. They further suggest possible mechanisms (e.g., paternal alcoholism history, coping motives) that may contribute to the development and maintenance of alcohol problems in criminal populations.
Cortisol Dysregulation and Cognitive Impairment in Abstinent Male Alcoholics
Authors: Errico Austin L. , King Andrea C. , Lovallo William R. , Parsons Oscar A. 
Published: April 2006

Background Alcoholics have impaired cortisol response to stress, indicating dysregulation in the extrahypothalamic systems responsible for activating cortisol secretion in response to stressor exposure. There is a growing literature indicating a relationship between hypothalamic‐pituitary‐adrenocortical axis activity and neurocognitive functioning. This study examined the hypothesis that dysregulation of the hypothalamic‐pituitary‐adrenocortical axis may be associated with some neuropsychological impairments in alcoholics.Methods Serum cortisol was obtained during cognitive testing and after exposure to cold pressor and mental arithmetic stress in 48 male alcoholics abstinent for 32 ± 6.7 days and in 30 controls; cortisol was also obtained from 18 of the alcoholic patients during withdrawal. Neurocognitive tasks included the Wechsler Memory Scale and Wisconsin Card Sorting Test. Relationships among alcoholics’ cognitive test scores, cortisol levels, and drinking practices were examined by correlation and regression analyses.Results Verbal memory deficits were more severe in alcoholics who had more withdrawals and ingested a higher typical quantity of alcohol during the prior year (p < 0.05). Higher levels of cortisol during withdrawal, an index of withdrawal severity, were associated with more errors on the Wisconsin Card Sorting Test (p < 0.005). As previously reported, the alcoholics had lower cortisol levels after stress compared with controls. Lower poststress cortisol levels were associated with poorer logical memory on the Wechsler Memory Scale and more errors on the Wisconsin Card Sorting Test (p < 0.05). Among controls, memory deficits occurred only in relation to higher poststress cortisol levels.Conclusions Poorer cognitive performance in alcoholics was related to more withdrawals, heavier alcohol consumption, and higher cortisol levels during a recent withdrawal. Alcoholics’ cognitive impairment was also related to attenuated stress cortisol responses. Altered stress regulation of the hypothalamic‐pituitary‐adrenal axis should be studied further as a potential factor related to impaired cognitive function in recovering alcoholics.
Co‐occurrence of Obsessive‐Compulsive Personality Traits in Young and Middle‐Aged Japanese Alcohol‐Dependent Men
Authors: Suzuki Kenji , Muramatsu Taro , Takeda Aya , Shirakura Katsuyuki 
Published: April 2006

Background Previous studies may have underestimated the potential importance of the prevalence of obsessive‐compulsive traits among persons with alcoholism. Although many studies have examined the characteristics of young alcoholics compared with middle‐aged alcoholics, none has compared the prevalence of obsessive‐compulsive traits in young and middle‐aged alcoholics.Methods This study compared the prevalence of obsessive‐compulsive traits (Leyton Obsessional Inventory) and depressive symptoms (Zung Self‐Rating Depression Scale) among young (n= 41) and middle‐aged (n= 34) hospitalized Japanese male alcoholics and in young (n= 28) and middle‐aged (n= 25) nonalcoholic subjects.Results Both young and middle‐aged male alcoholics reported more obsessive‐compulsive personality traits and depressive symptoms than their comparison groups. However, the alcoholic subjects’ obsessive‐compulsive personality traits were not related to their level of depressive symptoms.Conclusions Young and middle‐aged male Japanese alcoholics have more obsessive‐compulsive personality traits than nonalcoholic males of similar ages. Their alcohol‐related psychological and behavioral characteristics may derive, in part, from their obsessive‐compulsive symptoms.
Coping Among Individuals Seeking Private Chemical Dependence Treatment: Gender Differences and Impact on Length of Stay in Treatment
Authors: Kohn Carolynn S. , Mertens Jennifer R. , Weisner Constance M. 
Published: April 2006

Background Length of stay in treatment and coping skills are both predictive of chemical dependence and abuse treatment outcomes. However, little is known about whether coping strategies are related to length of stay in treatment. Because predictors of length of stay in treatment vary by gender, it also may be reasonable to expect gender differences in coping strategies as well as in the relationship between coping and LOS in treatment.Methods We examined gender differences in baseline coping strategies, and coping strategies as predictors of length of stay in treatment, among 747 (433 men, 314 women) individuals who entered chemical dependence and abuse treatment in a private, managed care facility.Results Women reported using more emotional discharge (behavioral attempts to reduce tension by expression of negative feelings), cognitive avoidance (cognitive attempts to avoid thinking realistically about the problem), resigned acceptance (cognitive attempts to react to the problem by accepting it), and seeking support/guidance (behavioral attempts to seek information, guidance, or support). Gender differences for emotional discharge disappeared after we controlled for depressive symptom and drug problem severities. Greater use of seeking alternative rewards (behavioral attempts to get involved in substitute activities and create new sources of satisfaction), less use of emotional discharge, and older age were significant predictors of longer length of stay, with no gender differences found.Conclusions This study provides evidence for identifying and decreasing the use of emotional discharge early in treatment, possibly through the use of intervention strategies such as anger management, cognitive restructuring, or motivational interviewing, as well as encouraging an increase in participation in alternative activities.
Serum Sialic Acid as a Marker of Alcohol Consumption: Effect of Liver Disease and Heavy Drinking
Authors: Romppanen Jarkko , Punnonen Kari , Anttila Petra , Jakobsson Tuula , Blake Joan , Niemelä Onni 
Published: April 2006

Background Serum sialic acid (SA) has been suggested as a new marker of alcohol consumption. There are, however, only a few studies on the clinical value of such measurements. The relationship between serum SA and liver disease is also unknown.Methods We determined serum SA concentrations in a sample of 51 alcoholics and 20 healthy controls by using high‐performance liquid chromatography with an anion‐exchange column and pulsed amperometric detection. The alcoholic sample included 32 patients with liver disease, the severity of which was assessed by previously established combined clinical, laboratory, and morphological indices. In addition, there were 19 heavy drinkers without significant liver disease despite a well documented history of excessive alcohol consumption.Results The (mean ± SD) SA concentrations (1.449 ± 0.3019 mmol/liter) were significantly higher in the alcoholics than in the healthy controls (1.154 ± 0.1702 mmol/liter). With the optimal cutoff limit for serum SA (1.425 mmol/liter), a specificity of 1.00 and sensitivity of 0.51 were obtained. The diagnostic accuracy of serum SA according to receiver operating characteristic analysis was good, with the area under the curve being 0.805 (0.052). Unlike the traditional serum markers of alcohol consumption (γ‐glutamyl transferase, carbohydrate‐deficient transferrin, and aspartate amino transferase), serum SA was not found to be different between the alcoholics with or without liver disease.Conclusions Our study suggests that serum SA is a sensitive marker of excessive alcohol consumption. Such measurements may also prove to be of value in conditions in which the results of the traditional markers reflect the severity of liver disease rather than alcohol consumption.
Accentuated Decrease in Social Interaction in Rats Subjected to Repeated Ethanol Withdrawals
Authors: Overstreet David H. , Knapp Darin J. , Breese George R. 
Published: April 2006

Background Previous work has shown that repeated withdrawals from chronic ethanol exposure can kindle seizures in rodents. In this article, the effects of a three‐cycle model of ethanol exposure and withdrawal on the social interaction test of anxiety are summarized.Methods Rats were exposed to ethanol (7% or 4.5%) diets over three periods of 5 days, with 2 days of withdrawal between cycles. Between 5 and 6 hr after the ethanol was removed, pairs of rats were placed in open field chambers for the assessment of social interaction behavior and locomotor activity.Results After the third cycle of ethanol (7%) presentation, both male and female rats exhibited lower social interaction behavior (more anxiety) and activity than after a single cycle. Rats exposed to a similar amount of ethanol but tested while ethanol was still available did not exhibit a reduction in social interaction. The decrease in social interaction was still present for up to 24 hr but had disappeared by 48 hr after ethanol was withdrawn. When rats were allowed 8 or 16 days to recover from the effects of the three‐cycle protocol, a further exposure to 5 days of 7% ethanol diet resulted in a reduction in social interaction on withdrawal similar to that seen from the three‐cycle protocol. In contrast, rats exposed continuously to 7% ethanol diet for 15 consecutive days exhibited higher levels of social interaction when maintained on control diet for 8 or 16 days and then reexposed to ethanol. Rats that were exposed to the three‐cycle protocol and allowed 32 days to recover before being reexposed to ethanol still had a partial deficit in social interaction. Finally, animals subjected to repeated withdrawals from 4.5% ethanol exhibited a reduction in social interaction without a change in activity after the final withdrawal from ethanol, whereas rats exposed continuously to a 4.5% ethanol diet did not exhibit a reduction in social interaction or activity. Neither blood ethanol concentrations nor changes in body weight could account for these behavioral differences.Conclusion Repeated withdrawal from ethanol can lead to accentuated or more persistent anxiety‐like behavior in rats, as indicated by a decrease in social interaction. The withdrawal‐induced decrease in locomotor activity is not accentuated by repeated withdrawals. This model of repeated withdrawals from ethanol may prove useful in defining the neurochemical basis of this accentuation.
Brain Catalase Inhibition Blocks Ethanol‐Related Decrease of Blood Luteinizing Hormone Levels in Mice
Authors: Sanchis‐Segura Carles , Aragon Carlos M. G. 
Published: April 2006

Background It has been demonstrated that ethanol decreases blood luteinizing hormone (LH) levels in rodents. This effect seems to be produced by the capacity of ethanol to release β‐endorphins from the hypothalamic arcuate nucleus and, in a second step, by a μ‐receptor–mediated inhibitory effect of these peptides on hypothalamic LH‐releasing hormone‐synthesizing neurons. However, it has been reported that, in primary hypothalamic cultures, the ethanol‐produced β‐endorphin release is mediated by the enzyme catalase. Therefore, the aim of this study was to assess whether catalase inhibition modifies ethanol effects on blood LH levels.Methods Swiss albino mice were pretreated with the catalase inhibitor 3‐amino‐1,2,4‐triazole (AT; 0.0–0.5 g/kg) and, 3.5 hr later, saline, ethanol (2.5 g/kg), or morphine (30 mg/kg) was administered. Blood samples were collected 2 hr after ethanol administration, and LH levels were immunoenzymatically assayed.Results The catalase inhibitor AT dose‐dependently blocked the ethanol‐produced decrease in blood LH levels without altering those observed after saline or morphine administration. This effect was highly correlated with the decrease in brain catalase activity produced by AT.Conclusions These results show an antagonistic effect between AT and ethanol on blood LH levels and suggest a role of brain catalase activity on this effect of ethanol. Data are discussed in terms of a possible functional relationship between brain catalase and β‐endorphins in the mediation of some of the psychopharmacological consequences observed after ethanol administration.