The fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was incorporated into myelin and synaptic plasma membrane fractions prepared from mouse brain. The absorption-corrected fluorescence and polarization of the fluorescent probe a molecule and the membrane absorbance were measured simultaneously, using a computer-centered spectrofluorimeter. In vitro exposure of synaptic membranes to ethanol (25-100 mM) decreased all three parameters in a dose-dependent manner. The order of sensitivity was: corrected fluorescence greater than or equal to polarization much greater than absorbance. Myelin was not affected by these concentrations of ethanol, indicating a selective effect on synaptic membranes. The polarization of fluorescence of DPH in synaptic membranes was also decreased by tert-butanol, pentobarbital, and cis- and trans-vaccinic acid. The results suggest that ethanol and related drugs perturb the hydrophobic interior of synaptic membranes. These compounds also increased the exposure of synaptic sulfhydryl groups and inhibited the depolarization- and ATP-dependent uptake of calcium by synaptosomal preparations. These results suggest that the perturbation altered the conformation of synaptic proteins and inhibited the transport of calcium by synaptosomal membranes.
Many animal models have been used for alcoholism research. No single model is suitable for all types of research about alcohol, its actions and abuse. This article surveys the varieties of models that have been used and categorizes them into classes called "chronic", "reinforcement" and "genetic" models and discusses the strengths, weaknesses and applications of each group. The diversity and scope of alcoholism offers unique challenges to the conduct of laboratory research with experimental animals. Animal models (AM) of the disease would have to encompass a broad range of variables No single model can incorporate all aspects of the disorder nor fulfill the needs of all research projects. Consequently, many different AM have been proposed. This review classifies those models, describes their underlying premises, experimental applications and their relative strengths and limitations. The scientific literature contains numerous examples of essentially sound experiments that lack credibility because of weaknesses in design aspects associated with the selection or use of AM. The alcoholism literature cannot be excluded from that statement. There are many examples of the inappropriate use of AM in alcoholism research and of poorly conceived attempts to use models developed for specific experimental applications in experiments requiring an entirely different approach. Furthermore, a persistent problem that is unique to alcoholism research relates to providing appropriate controls. Since alcohol (ALC) has caloric as well as pharmacological effects, dual controls must be established. The caloric effects of ALC can alter an animal's nutritional state in important ways. Therefore, studies involving more than one or two ALC doses must provide adequate controls for both the pharmacological and the non-specific nutritive effects. Unfortunately, such controls are often difficult to establish and validate.
Tolerance to ethanol, as assessed by loss of the righting reflex or by improved performance in the aerial righting reflex test, was only observed in animals which did not show signs of a withdrawal reaction. With long exposure periods to ethanol vapor, tolerance was no longer present in animals exhibiting withdrawal reactions. These data are consistent with the hypothesis that a reversal of tolerance precedes prior to the development of physical dependence on ethanol.
Administration of a single large dose of ethanol (5 g/kg) to rats elevates the rates of ethanol metabolism and of oxygen consumption in perfused livers in 2–3 hr. Pretreatment with the antithyroid drug propylthiouracil (PTU) for 10 days abolished both of these effects. Under all treatment conditions studied (controls; PTU-pretreatment; acute ethanol treatment; PTU-pretreated + acute ethanol treatment), a significant correlation between ethanol metabolism and oxygen consumption was observed (r = 0.86). It is concluded that a normal thyroidal state is required to evoke the swift increase in alcohol metabolism (SIAM) and an elevation of oxygen consumption.
Data from two recent National Center for Health Statistics (NCHS) surveys which included alcohol consumption questions are described. These surveys are the Health and Nutrition Examination Survey (HANES I), providing alcohol consumption, dietary recall, health and demographic data for over 20,000 respondents; and the Health Habits Section of the 1977 Health Interview Survey (HIS) which provides responses of 23,000 people on drinking behavior and health factors such as smoking, physical disabilities, and dietary habits. Drinking data from these surveys are limited but of sufficient accuracy to be useful for cross-classification of drinking with health, socio-economic and demographic variables. Drinking patterns correlate reasonably well with those reported in other national surveys. Selected findings show that patterns of drinking and dietary intake are similar at national and regional levels, with the South remaining the region lowest in alcohol consumption levels. Surveys consistently under-report alcohol quantities expected from sales in all regions; potential reasons for this are discussed. Highest consumption is reported by males (3 to 4 times that of females), those with European national origins, those who are working or in school (college) rather than those who are retired or keeping house, and those between 25 and 64 years old. Beer remains the beverage of choice, particularly among those who are the heaviest drinkers. The potential for future analyses of drinking behavior and its health implications is explored, and areas for further investigation are suggested. Data preparations have been completed so that information on alcohol consumption can be more readily related to medical history, medical examination, laboratory findings, disability, and health care data in these surveys.
Many studies have demonstrated that the ability of alcohols and other intoxicant-anesthetics to affect biochemical, physiological, and behavioral processes rests in their hydrophobicity. This means that potency is determined by the ability of the drug to move from a water phase into a lipid or membrane phase. In more precise terms, anesthetic effects are correlated with the volume occupied by the anesthetic molecules within the membrane. Although the anesthetic effects, particularly the inhibition of nerve condition, have been used most frequently in establishing this correlation, the intoxicating effects (i.e., ataxia) of a series of alcohols had also been correlated with their membrane partitioning. These results suggest that the intoxicating, as well as anesthetic, effects of ethanol and related drugs are due to their penetrating into hydrophobic regions of nerve membranes. The predominant hydrophobic region of biological membranes is the "sea" of lipid that surrounds "islands" of functional proteins. This leads to the postulate that intoxicant-anesthetics alter the physical properties of membrane lipids and thus affect neuronal function. To evaluate this hypothesis, we must consider the lipid composition of brain membranes, the importance of membrane lipids in neuronal function, the techniques available for the study of membrane physical properties, and the effects of ethanol on nerve membranes.
This article reviews the similarities and differences of alcoholism and drug abuse from a biopsychosocial perspective. Special emphasis is given to newer developments. In biology, the role of endorphins and isoquinolines is considered against the more traditionally recognized clinical differences between alcohol and drug disorders. Consideration is given to psychological themes such as the utility of the addictive personality concept, the impact of more sophisticated prevention strategies, and the combined treatment of alcoholics and drug abusers. Reports from social fields include a cross-cultural view of chemical dependence and an appraisal of legal and political trends which influence chemical use and the civil rights of chemical users. Recent developments in the biologic, psychologic and social sciences have solidified the impression that the chemical dependencies, for all their differences, share a number of important characteristics. The etiology of alcoholism and drug abuse has been attributed to biopsychosocial causes, currently a widely accepted hypothesis. From one perspective, this theory could be seen as a grab bag approach, since no specific universal cause has been discovered while many have been postulated. From another aspect, the hypothesis is a rational synthesis of present knowledge which finds no one etiological factor to be either preeminent or ubiquitous. This article presents in succession an overview of the biology, psychology and sociology of chemical dependence with emphasis on integrating newer developments with familiar knowledge.
The pattern of alcohol consumption and beverage preferences of heart patients were investigated in 3026 men and 760 women who have had coronary arteriography due to symptoms of coronary heart disease. The younger male heart patients (less than 40 years old) as a group had higher proportion of abstainers and heavy drinkers (more than six drinks daily) than the age-matched reference groups from the general population; the opposite was true for male patients over 60 years of age. The preference for hard liquor (more than 50% of total alcohol intake) tended to rise with age and extent of coronary artery occlusion. Wine as a preferred beverage was reported by approximately 10% of the male patients. The female patients had about twice as high prevalence of abstainers as the male patients.
Oklahoma Indian tribes are ranked according to five problem drinking indicators and five socioeconomic indices. The relationship between the tribes' prevalence of alcohol problems and socioeconomic conditions is examined. Unfavorable socioeconomic conditions predicted high rates of alcohol problems, but more favorable conditions did not predict low rates. Social controls may be more important than socioeconomic conditions in controlling alcohol problems among Oklahoma Native Americans. In a previously published study we found that Native American tribes in Oklahoma varied dramatically in the extent to which they suffered from alcohol problems. In this followup study we have sought explanation for these large differences by comparing the socioeconomic conditions of the tribes to their rates of alcohol related problems. The relationship between socioeconomic conditions and alcohol problems has received considerable attention in the literature. Popham, et. al. found that when the price of beverage alcohol relative to average disposable (real) income is high, indices of alcohol consumption and alcoholism are usually low, and vice versa. In a similar vein, Edwards et. al. suggested that alcoholism is likely to increase the risk of death more in upperclass than in lowerclass alcoholics. On the other hand, others have blamed economic deprivations for high rates of problem drinking, especially among disadvantaged minorities. Price suggested that Indian societies which had little access to economic opportunities have more drinking problems than those with great access. Caravedo found that socioeconomic deprivation is a primary factor in both the etiology and the medical consequences of alcoholism.
Authors predicted that adult alcoholics with relatively higher scores on obsessive-compulsive drinking subscale of Alcohol Use Inventory (AUI-4) and psychasthenia scale of Minnesota Multiphasic Personality Inventory (MMPI-7) would be better candidates for successful completion of traditional outpatient treatment. Both tests were administered to 89 successively admitted outpatients who were tracked through treatment and later classified as dropouts (premature unilateral termination of treatment, N = 57), mutuals (patient-therapist agreement on appropriate termination, N = 22), or open cases (patients still in treatment at end of 6 months, N = 10). AUI-4, but not MMPI-7, successfully identified dropouts, mutuals, and open cases, and significantly differentiated between dropouts and all other patients. AUI-4 and MMPI-7 were significantly and positively correlated, and AUI-4, but not MMPI-7, was significantly and positively related to number of therapy sessions.
Tremor measurements were obtained from 12 male volunteers before and during ethanol intoxication. The tremor recorded during extension and flexion of the hand is called physiological action tremor (PAT) and shares many of the same frequency, amplitude, and electromyographic characteristics reported for withdrawal tremor (WT). This report focuses on the relationships of these two tremors and presents further evidence to consider that PAT and WT might be controlled by the same mechanisms.
: The distribution of 14C-alpha-aminoisobutyric acid (AIB), administered intravenously, in maternal, fetal and placental tissues was examined in the rat on gestation-day 21. Ethanol consumption during gestation (day 6 through 21) significantly reduced the uptake of AIB by the placenta and fetus while exerting no influence on maternal tissue AIB uptake. The concentration of fetal plasma free histidine was decreased 50% as a result of maternal ethanol ingestion, but the free histidine level of maternal plasma was not altered. Since no effect on protein content of fetal tissue could be detected, it is speculated that reduced histidine to the fetus might significantly alter the amounts of histamine and carnosine formed via their precursor. The significance of these findings in relation to the Fetal Alcohol Syndrome is discussed.
Neonatal withdrawal symptoms in 15 cases of fetal alcohol syndrome with maternal intoxication at time of delivery, reported in 9 studies, are compared with symptoms reported in 138 cases of neonatal narcotic withdrawal. Seen frequently in ethanol but rarely in narcotic withdrawal are abdominal distention and opisthotonos. Seen frequently in narcotic but rarely in ethanol withdrawal are high pitch cry, frequent yawning, excessive sucking, mottling of the skin, excoriation, nasal stuffiness, excess sweating, sleeplessness and diarrhea. Seen frequently in both are increased muscle tonicity and tremors; however, convulsions are rare in narcotic yet are fairly frequent in neonatal ethanol withdrawal.
