A behavioral economic analysis of concurrent ethanol- and water-reinforced responding in different preference conditions

BACKGROUND: The reinforcing properties of orally self-administered drugs have been evaluated by using choice procedures. The preference for the drug over a nondrug alternative has indicated that the drug has greater value than the nondrug alternative as a reinforcer at some drug concentrations. However, at large drug concentrations, the fluid deliveries of the drug may be equal to or less than those of the nondrug alternative, whereas the actual drug intake (milligrams per kilogram of body weight) may continue to increase. In this study, we used behavioral economics to evaluate the reinforcing strength of ethanol in conditions where baseline ethanol fluid deliveries were greater than, equal to, or less than those of the concurrently available water. METHODS: Four male rhesus monkeys were allowed access to ethanol (2%, 8%, or 32%) and water for 2 hr/day under a fixed ratio (FR) 4 reinforcement schedule. At each ethanol concentration, the FR for both fluids was gradually increased to FR 64. RESULTS: During the FR 4 schedule, the fluid deliveries of ethanol at 2%, 8%, and 32% were greater than, equal to, and less than those of water, respectively. When the FR was increased at 2% ethanol, fluid deliveries and responding decreased for both the ethanol and water. When the FR was increased at 8% ethanol, water fluid deliveries and responding decreased more rapidly than did those of ethanol. When the FR was increased at 32% ethanol, the ethanol fluid deliveries remained the same across all FRs, whereas water fluid deliveries decreased rapidly. At 8% and 32% ethanol, the responding for ethanol, relative to water, increased dramatically. CONCLUSIONS: In behavioral economic terms, demand for ethanol was more inelastic regardless of whether the ethanol or water maintained more absolute fluid deliveries at baseline FRs. Therefore, researchers should examine the reinforcing effects of ethanol in a variety of concentration and schedule conditions rather than drawing inferences regarding reinforcing effects simply based on a preference measure.     

Upregulation of beta-catenin levels in superior frontal cortex of chronic alcoholics

Background: Chronic and excessive alcohol misuse results in neuroadaptive changes in the brain. The complex nature of behavioral, psychological, emotional, and neuropathological characteristics associated with alcoholism is likely a reflection of the network of proteins that are affected by alcohol‐induced gene expression patterns in specific brain regions. At the molecular level, however, knowledge remains limited regarding alterations in protein expression levels affected by chronic alcohol abuse. Thus, novel techniques that allow a comprehensive assessment of this complexity will enable the simultaneous assessment of changes across a group of proteins in the relevant neural circuitry. Methods: A proteomics analysis was performed using antibody microarrays to determine differential protein levels in superior frontal cortices between chronic alcoholics and age‐ and gender‐matched control subjects. Seventeen proteins related to the catenin signaling pathway were analyzed, including α‐, β‐, and δ‐catenins, their upstream activators cadherin‐3 (type I cadherin) and cadherin‐5 (type II cadherin), and 5 cytoplasmic regulators c‐Src, CK1ε, GSK‐3β, PP2A‐Cα, and APC, as well as the nuclear complex partner of β‐catenin CBP and 2 downstream genes Myc and cyclin D1. ILK, G_α1, G_β1, and G_β2, which are activity regulators of GSK‐3β, were also analyzed. Results: Both α‐ and β‐catenin showed significantly increased levels, while δ‐catenin did not change significantly, in chronic alcoholics. In addition, the level of the β‐catenin downstream gene product Myc was significantly increased. Average levels of the catenin regulators c‐Src, CK1ε, and APC were also increased in chronic alcoholics, but the changes were not statistically significant. Conclusion: Chronic and excessive alcohol consumption leads to an upregulation of α‐ and β‐catenin levels, which in turn increase downstream gene expressions such as Myc that is controlled by β‐catenin signaling. This study showed that the β‐catenin signal transduction pathway was upregulated by chronic alcohol abuse, and prompts further investigation of mechanisms underlying the upregulation of α‐ and β‐catenins in alcoholism, which may have considerable pathogenic and therapeutic relevance.     

Acute Alcohol Effects on Inhibitory Control and Implicit Cognition: Implications for Loss of Control Over Drinking

Alcohol impairs inhibitory control, and it alters implicit alcohol cognitions including attentional bias and implicit associations. These effects are seen after doses of alcohol which do not lead to global impairments in cognitive performance. We review studies which demonstrate that the effects of alcohol on inhibitory control are associated with the ability of alcohol to prime alcohol‐seeking behavior. We also hypothesize that alcohol‐induced changes in implicit alcohol cognitions may partially mediate alcohol‐induced priming of the motivation to drink. Based on contemporary theoretical models and conceptualizations of executive function, impulsivity, and the motivational salience of alcohol‐related cues, we speculate on other aspects of cognition that may underlie alcohol’s effects on alcohol seeking. Inconsistencies in existing research and priorities for future research are highlighted, including dose effects and the potential interactions between chronic heavy drinking and the acute effects of alcohol on these cognitive processes.     

Leukopenia in alcoholics

Nine leukopenic episodes were studied in six alcoholics without coexistent bacterial infection, splenomegaly or megaloblastic erythropoiesis. The number of mature neutrophils was reduced in the blood and bone marrow, and the marrow granulocyte reserve was decreased. Serum unsaturated vitamin B₁₂-binding capacities were low, and muramidase activities were normal. Serum vitamin B₁₂ was normal; serum folate was low in five and normal or high in three. The reduced leukocyte count in blood and bone marrow, as well as the decreased granulocyte reserve and serum unsaturated vitamin B₁₂-binding capacity, returned to normal within two weeks without specific therapy. These findings suggest that prolonged and excessive consumption of alcohol may suppress myelopoiesis in man.     

Sleep-disordered breathing in alcoholics

Sleep apnea and related disorders contribute to disturbed sleep in abstinent alcoholics. In an earlier report from our group, sleep-disordered breathing was common and increased with age in a cohort of 75 abstinent alcoholics. We now report an extension of the previous work that includes studies of an additional 103 abstinent alcoholics undergoing treatment for alcoholism (total sample = 188) and a comparison group of 87 normal subjects. The presence and severity of sleep-disordered breathing was assessed with polysomnography. Among the alcoholics, sleep-disordered breathing (defined as 10 or more apneas plus hypopneas per hour of sleep) was present in 3% of 91 subjects under age 40, 17% of 83 subjects age 40 to 59, and 50% of 14 subjects age 60 or over. Subjects with sleep-disordered breathing were more likely to be male and had more severe sleep disruption and nocturnal hypoxemia and more complaints related to daytime sleepiness than subjects without sleep-disordered breathing. In a multiple linear regression analysis, age and body mass index were significant predictors of the presence of sleep-disordered breathing, whereas smoking history and duration of heavy drinking were not predictors after controlling for the effects of age and body mass index. Our findings suggest that sleep-disordered breathing contributes significantly to sleep disturbance in a substantial proportion of older alcoholics and that symptomatic sleep-disordered breathing increases with age in alcoholics. Sleep-disordered breathing, when combined with existing cardiovascular risk factors, may contribute to adverse health consequences in alcoholics.     

Pulmonary function in alcoholics

Twenty-three chronic alcoholics were investigated by means of pulmonary function studies. All 23 patients had respiratory symptoms. Clinically, 21 (91 per cent) of 23 patients were diagnosed as having chronic bronchitis, and 14 patients (60 per cent) had dyspnea. The maximal mid-expiratory flow and single breath diffusing capacity for carbon monoxide (SBDCO) were abnormal in 16 (70 per cent) and 14 (61 per cent) patients, respectively. Twenty-two of 23 patients had one or more abnormal function. The total lung capacity, residual volume, vital capacity, 1 second forced expiratory volume and SBDCO progressively declined with increasing alcohol consumption. An attempt was made to separate the pulmonary effects of alcohol from (1) the effects of previous pulmonary infections, (2) the effects of cigarette smoking, and (3) the effects of cirrhosis of the liver. The data suggest that either alcohol itself through some unknown mechanism may be a causative agent in producing lung disease or that alcohol makes a higher percentage of the population susceptible to the harmful effects of cigarette smoking.     

Pancreatic secretion in chronic alcoholics

To gain further insight on the effects of alcohol on human pancreatic enzyme secretion, we tested the effects of a 12% (v/v) alcohol solution, wine, and a glucose sclution added to a meal on trypsin output in duodenal aspirate of nonalcoholic volunteers and compared the results to those of chronic alcoholics. Plasma concentrations of gastrin, cholecystokinin, and pancreatic polypeptide were monitored pre-and postprandially. Similar blood alcohol concentrations were determined in nonalcoholics and alcoholics following wine and the alcohol solution. Nonstimulated trypsin output (basal) was higher in alcoholics but not significantly so when compared to nonalcoholics. However postprandial trypsin output, 2014±301 mg/5 hr was significantly greater in alcoholics (P<0.05) compared to nonalcoholics 1271±118 mg/5 hr. Alcohol and wine when added to the meal significantly (P<0.05) inhibited trypsin output in both groups. Basal and postprandial levels of gastrin and cholecystokinin were similar in nonalcoholics and alcoholics. Basal plasma pancreatic polypeptide levels were similar in both groups, but the postprandial increments in pancreatic polypeptide levels observed in nonalcoholics were not observed in alcoholics. We conclude that chronic alcoholics have increased postprandial pancreatic enzyme secretion, and that this secretion, as that of nonalcoholics, can be affected by alcohol or wine. The postprandial hypersecretion of enzymes in alcoholics is not related to increased plasma levels of cholecystokinin or gastrin. It is possible that the impaired release of pancreatic polypeptide may participate in the mechanism for increased pancreatic enzyme secretion in chronic alcoholics.This work was supported by grant AA 07676-01A1 from the Alcohol, Drug Abuse and Mental Health Administration and in part by a grant (GCRC RR-43) from the General Clinical Research Centers Program of the Division of Research Resources, National Institute of Health.     

Diastolic function impairment in alcoholics

BACKGROUND: Chronic excessive ethanol consumption exerts a deleterious effect on the myocardium. Although the effects of chronic alcoholism on systolic cardiac function are well known, diastolic involvement has been evaluated only partially. Therefore, we determined the presence of left ventricular diastolic impairment in chronic alcoholics and its relation with simultaneous systolic dysfunction. We also assessed the influence of ethanol consumption in diastolic impairment. METHODS: Thirty-five alcoholics with cardiomyopathy (ejection fraction < or = 50%) and 77 alcoholics with normal systolic function (ejection fraction > 50%) were evaluated. Assessment of New York Heart Association functional class, history of ethanol intake, technetium-99m radionuclide angiocardiography, and bidimensional Doppler echocardiography with evaluation of systolic and diastolic left ventricular function were performed. RESULTS: Diastolic function impairment was present in one third of the alcoholics without cardiomyopathy, compared with two thirds of the patients with cardiomyopathy (p < 0.01). A pseudonormalization phenomenon of diastolic function was observed in patients with more advanced systolic dysfunction (ejection fraction < 32%). The deterioration of the diastolic parameters correlated with ethanol consumption, regardless of age (r = 0.44, p < 0.001 for ratio of peak velocity of the transmitral flow in early diastole and peak velocity of atrial contraction flow, with lifetime dose of ethanol). CONCLUSIONS: There seems to be a dose-dependent effect of ethanol on systolic and diastolic heart function. Diastolic function impairment is present in one third of alcoholics with normal systolic function and is even more frequent when systolic dysfunction coexists.     

Influence of Antisocial and Psychopathic Traits on Decision-Making Biases in Alcoholics

Background:  Although decision-making processes have become a principal target of study among addiction researchers, few studies have specifically examined decision-making among individuals with alcohol dependence (AD) and findings to date are mixed. The present study examined the relationship between AD and decision-making, and tested whether different facets of antisocial and psychopathic traits explain this association.
Methods:  Participants were men with AD ( n  =   22), AD and comorbid antisocial personality disorder (AD + ASPD; n  =   17), or a history of recreational alcohol use, but no current or lifetime symptoms of a substance use disorder, conduct disorder, or ASPD ( n  =   21). Decision-making was tested using the Iowa Gambling Task (IGT).
Results:  Across groups, participants reported similar levels of awareness of the contingencies of the task, but the AD groups with and without ASPD had poorer IGT performance compared with controls ( p  < 0.05). A block-by-block analysis revealed that while AD had slow but steady improvement across the task, AD + ASPD exhibited initial improvement followed by a significant decrease in advantageous decision-making during the last 20 trials ( p  < 0.05). This was further confirmed via evidence that impulsive/antisocial personality traits but not psychopathic traits mediated poor IGT performance beyond ASPD diagnosis.
Conclusions:  Alcohol-dependent males favored risky choices regardless of whether they met criteria for ASPD. However, decision-making deficits were more pronounced among those with ASPD, and personality traits characterized by impulsive and antisocial tendencies mediated the relationship between AD and decision-making.     

Echocardiographic abnormalities in chronic asymptomatic alcoholics

Alcohol abuse is a frequent contributor to elevated blood pressure, but the literature is ambiguous about the role of hypertension in producing left ventricular dysfunction. Fifty asymptomatic male alcoholics admitted for detoxification were studied using echocardiograms and systolic time intervals. Alcoholics were separated into Group I (28 with hypertension) and Group II (22 without hypertension). Forty-four patients had analyzable echocardiograms and were compared to 29 nonalcoholics. Group III consisted of 14 nonalcoholics with hypertension. Group IV consisted of 15 normotensive nonalcoholics (controls). The ejection fraction and shortening fraction were reduced in Group I (p less than 0.05). Hypertensive alcoholics had increased left ventricular mass indices but less than hypertensive nonalcoholics. Left ventricular wall stress was compared to mass as an index of ventricular compensation. The wall stress to mass index for hypertensive alcoholics was 1.65 as compared to 1.43 for the controls. Alcoholics without hypertension had a wall stress to mass ratio of 1.54. Hypertensive patients had a reduced wall stress to mass ratio of 1.38 when compared to controls. These data suggest an inappropriate compensatory response to afterload. Alcohol and hypertension combined may be more harmful to left ventricular function than either disease alone.