The resistance of glioma cells to radiations may be diminished by previous ethanol or oxygen treatment. When rat glioma C6 cells were treated with either 50 mM or 100 mM ethanol in the culture medium before X ray irradiation (1000 rads), the surviving cells decrease two weeks later by about 40% compared with irradiated non treated cells. We suggest that the greater cell death after irradiation of alcohol treated glioma cells in culture may partially result from an accumulation of cytotoxic O = 2 radicals, since superoxide dismutase activity was reduced under these conditions.
Mice were injected with 0, 107, 215, 430, or 1720 mg/kg of ascorbic acid. Thirty min later they were tested for ethanol (3.5 g/kg) induced sleep time. Brain ethanol levels were determined upon awakening. Another group of mice were tested for apomorphine (3 mg/kg) induced locomotor activity also 30 min after ascorbic acid injection. Ascorbic acid in doses above 215 mg/kg augmented ethanol sleep time up to 210% at the highest doses, the increase being significant from 430 mg/kg. Brain ethanol levels upon awakening were reduced by ascorbic acid treatment; this reduction was significant at 1720 mg/kg dose. Ascorbic acid decreased apomorphine-induced locomotor activity in a dose response manner that paralleled the ascorbic acid increase of ethanol sleep time. At the highest dose of ascorbic acid, apomorphine-induced locomotor activity was completely eliminated. It is suggested that ascorbic acid increases brain sensitivity to ethanol by lowering the activity of dopamine receptors.
This report presents a set of findings from a three wave 36 month longitudinal study on the use of cigarettes, alcohol, marijuana/hashish and other drugs by a population of children and adolescents ranging in age from 9 to 17 at the time of first interview. Gross differences in percentages of subjects reporting using substances across the three data collection intervals are found to be quite small. However, when these differences are examined in detail, it is found that a good deal of initiation of use by some subjects and curtailing of use by others stands behind the relatively small net changes in use from one interval to another. Escalation in substance use, from less mood altering to more mood altering substances, is found to exist, but to appear far less frequently than "initial" multiple drug use. Finally, "intensity" of use of one substance is found to be somewhat related to age and very strongly related to the use of other substances. Limitations of findings due to episodic rather than continuous monitoring of substance use are noted.
Rats (N=6) were trained to discriminate 3.0 mg/kg i.p. phencyclidine (PCP) from saline in a 2-lever fixed-ratio 32 operant discrimination procedure for food presentation. Generalization tests were conducted with other doses of PCP as well as with various doses of the stereoisomers of dioxadrol. Dose-dependent PCP-like discriminative stimulus effects were obtained with dexoxadrol but not with levoxadrol, however overall rates of responding were decreased to a comparable extent by 30 mg/kg of both compounds. PCP was 3.6 times more potent than dexoxadrol in producing stimulus control of responding. These data provide some evidence for stereoselectivity of action for dioxadrol, however nonPCP-like effects of levoxadrol are present at doses only 3 times greater than those doses of dexoxadrol that result in PCP-lever responding. Therefore, absolute stereospecificity beyond 3-fold cannot be demonstrated by these data.
Survey data was analyzed to examine the relationship between alcohol consumption and systolic blood pressure (SBP) in the general population. Among older people, SBP is higher for heavier drinkers. Among females, SBP is slightly lower for the light drinkers than for abstainers.. These effects are measured with obesity, race, and menopause, use of birth control pills, smoking, and anxiousness held constant. The reasons for these effects are not clear.
Rats treated acutely with ethanol showed a significant increase in biliary bilirubin secretion and in serum bilirubin levels (compared to saline treated controls); no difference was found in bile acid secretion. In rats fed ethanol chronically (36% of total energy for 4-6 weeks) there was a significant increase in the secretion of bilirubin and bile acids when compared to pair fed controls. We observed this effect either in the presence or in the absence of alcohol in the blood at the time of the experiment. The presence of ethanol in the blood, however, resulted in higher biliary and serum bilirubin levels. The increase in bile acid secretion involved selectively di- (but not tri-) hydroxy bile acids. Since increased secretion of unconjugated bilirubin favors pigment gallstones formation, it can be postulated that ethanol contributes to the pathogenesis of cholelithiasis by enhancing the biliary secretion of the pigment.
We examined the effect of acute and chronic ethanol administration on brain and liver gamma-hydroxybutyric acid (GHB), the effect of pyrazole on the ethanol-GHB interaction, and the effect of acetaldehyde on brain and liver GHB. Ethanol produced a marked increase in liver GHB but had no effect on GHB in brain. The ethanol effect in liver was not blocked by pyrazole. Acetaldehyde had no effect in brain or liver on GHB.
The chronic consumption of alcohol has been correlated with the development of cardiomyopathy and dysrhythmias. These disorders may be secondary to changes in the outflow of the autonomic nervous system. This study looked at the changes in cardiac cell responsiveness to carbamylcholine (CBL) and the concentration of muscarinic receptors. The studies were carried out on hearts excised from male Long-Evans hooded rats, pair-fed on ethanol (E) or control (C) liquid diet. The ethanol diet supplied 35-39% of calories as ethanol. The studies were carried out after 8-10 wks or 18-20 wks on the diet. Ventricular muscarinic receptors were measured using (-)-[3H]quinuclidinyl benzilate (QNB). These studies showed no significant difference in muscarinic receptor concentration or the dissociation constant for [3H]QNB binding after 8-10 wks or 18-20 wks of E ingestion. Electrophysiologic studies of chronotropic responsiveness to CBL showed no significant difference between the E and C groups after 8-10 wks or 18-20 wks. The responsiveness of subsidiary pacemaker cells to CBL was not different between E and C groups at 18-20 wks. These data indicate that chronic E ingestion for up to 20 wks did not effect the cardiac muscarinic receptor concentration or cholinergic response.
Brain proteins of BALB/cBy mice were labeled for a period of 8 days by a single intraperitoneal injection of valine. Following this the mice received 10% ethanol and protein breakdown was estimated from the release of label from brain proteins. Ethanol intake resulted in a significant inhibition of cerebral protein breakdown in vivo as measured in whole brain and in subcellular brain fractions (myelin, synaptosomes, mitochondria, microsomes, and nuclei). The intake of 10% ethanol for 4.5 months resulted in minor alterations in amino acid levels; increase in some and decrease in others were observed in plasma and brain, but most of the changes were not significant (P greater than 0.05). The uptake of AIB in brain was decreased 17% by prolonged ethanol intake.
Five different alcoholic beverages were tested in rats to determine if congener content contributed to the hypothermia or motor impairment produced by the beverages. Solutions of cognac, scotch, tequila, vodka, and commercially supplied ethanol were diluted with physiological saline to form solutions containing 16% w/v ethanol, as verified by gas chromatographic analysis. All beverages were administered in doses containing 0 (saline), 1.6, 3.2, 4.8, or 6.4 g/kg ethanol (gastric intubation) in test sessions separated by 7 days (repeated measures design, N = 8 rats per group). Measurements of rectal temperature and motor impairment (rotarod performance) made at 0, 60, and 120 minutes postinjection revealed no noteworthy differences in either measure at 60 or 120 minutes postinjection at any of the 4 doses tested. Thus, no evidence for a contribution of congeners to beverage effects was observed.
Adult C57/BL mice subjected to short term ethanol liquid diets exhibited significant increases in liver microsomal phosphatidylethanolamine methyltransferase activity(s) as well as changes in microsomal lipid composition. Specifically, increases in [3H]-methyl incorporation into phosphatidyl-N-monomethylethanolamine and phosphatidyl-N,N-dimethylethanolamine were observed suggesting increases in phospholipid methyltransferase I and the first methyl transfer reaction of phospholipid methyltransferase II. Labeling of phosphatidylcholine was not affected, however. Dietary supplementation with 2% choline reduced liver methyltransferase activities of both control and ethanol treated mice. The ethanol induced increase in methyltransferase activity returned to control values upon removal of ethanol from the diet for 24 hours. It is suggested that the increase in phospholipid methyltransferase activity after chronic ethanol treatment may be responsible, in part, for alterations in the activities of certain microsomal enzymes known to be influenced by ethanol.
Tail skin temperature (TST) response of morphine-dependent rats was evaluated as a potential in vivo assay for the activity of narcotic antagonists. Dependency was produced in rats by repeated subcutaneous implantation of morphine-containing pellets and TST was evaluated by thermistor probes attached to the dorsal surface of the tail. TST was determined prior to and following administration of either naloxone (NAL: 0, 0.01, 0.1, 0.5 or 1.0 mg/kg body weight); naltrexone (NALT: 0.001, 0.005, 0.01, 0.02 or 0.1 mg/kg body weight); or 6-Desoxy-6-methylenenaltrexone (DM-NALT: 0.001, 0.005, 0.01, 0.02 or 0.1 mg/kg body weight). Each of the narcotic antagonists caused a dose-dependent increase in tail skin temperature in morphine dependent rats. The initial TST increase was observed by 5 minutes and the maximal TST response occurred 15 to 25 minutes after drug administration. For each drug evaluated, a linear relationship was observed between the dose and maximal change in TST and between the dose and the area under the TST response curve. Determination of ED50 for the TST response revealed the expected relative potency for the narcotic antagonists evaluated: DM-NALT greater than NALT greater than NAL. Thus, the TST-response test is a rapid and quantitative bioassay for the evaluation of compounds for narcotic antagonistic activity.
Barbiturate physical dependence was produced by twice-daily administration of Na barbital to cats according to the "low" dose barbiturate protocol (Okamoto et al., J. Pharmacol. Exp. Ther. 207: 906, 1978). The duration of treatment was 1, 2, 3, 5, 9 or 14 weeks. Pharmacodynamic tolerance was assessed by relating the degree of neurofunctional impairment to the blood barbital concentration at the time when the functional test was performed. Evaluation of withdrawal was based on whole-animal observation and subjective assessment of overt withdrawal signs. Motor activity and withdrawal convulsions were monitored continuously by an activity recording device. It was found that the pharmacodynamic tolerance and physical dependence continued to develop throughout the treatment period and no apparent ceiling on these phenomena was observed. The "low" level chronic dosing merely prolonged the time required to develop physical dependence of severity comparable to that produced by shorter durations of "high" level chronic dosing.
The time courses of changes in levels of beta-hydroxybutyrate (BOHB), glucose (GLC), and glycogen (GLY) were measured hourly for 7 h after i.p. 2 g/kg ethanol (ETOH) in samples of liver, blood, and brain in 21 day old C57BL/6J mice. After acute ETOH, brain GLC remained at 2.1 mmol/kg for 2 h, fell to a low of 1.5 mmol/kg at 5 h, then rose slightly. Blood GLC remained near 8 mmol/kg until 3 h, then fell. Liver GLC fell steadily from 10.2 to 7.2 mmol/kg at 7 h. Brain GLY rose from 1.7 to 2.9 mmol/kg at 3 h, then fell steadily. Blood GLY increased from 2.7 to 4.6 mmol/kg at 2 h, then fell to 1.7 mmol/kg. Liver GLY decreased from 70 to 30 mmol/kg. BOHB changes were similar in all samples. BOHB in brain fell from 0.12 to 0.08 mmol/kg at 2 to 3 h; then rose steadily to 0.27 mmol/kg at 7 h. Blood and liver BOHB fell from 0.40 to 0.25 mmol/kg, then rose to 1.0 mmol/kg. In a previous study, susceptibility to audiogenic seizures after 2 g/kg ETOH was completely suppressed for up to 1 h, then susceptibility increased to a maximum at 5 1/2 h, when a period of potentiation was observed. In this study, brain GLY levels were increased during the period of protection, and brain GLC levels were decreased during the period of potentiation. Together, these data may lend support to an hypothesis of an indirect effect of ETOH on the brain, leading to changes in susceptibility to audiogenic seizures via changes in metabolite availability.
The effects of betacarbolines on guinea-pig isolated sinus nodes superfused with Tyrode's solution at 35 degrees C were analyzed. All analogs depressed the automaticity. The phase 4 of transitional fibers was depressed, in the absence of any change in maximum diastolic potential. The threshold for harmaline action was 10(-7)M. Dehydrogeneration of harmaline into harmine increased the potency. Removal of the methoxy group (harmane) did not modify the potency but accelerated the recovery. Substitution of the methoxy group by a hydroxy group (harmalol and harmol) reduced markedly the potency of harmaline and harmine, respectively.
This paper presents a critical discussion of the definitions, conceptual models, and methodological issues that researchers should consider in studies of sociocultural influences on drinking practices and problems. In particular, these concerns are related to studies of American Indian and Alaskan Native people. In an effort to avoid overgeneralized explanatory statements, it is recommended that efforts be made to study more specific aspects of such loosely defined terms as culture, alcoholism, and "Indianness." Research in this area might usefully be guided by parsimonious conceptual models developed and investigated in the dominant culture; however the extent to which relationships observed within one group generalized to another group remains an empirical question. While there may be a common set of operationalizing variables and collecting valid data cannot be assumed to have equal applicability with different subgroups. By remaining sensitive to the methodological implications of sociocultural differences, investigators can more accurately clarify the processes by which complex biological, psychological, and sociocultural factors influence alcohol use and misuse in any individual or group.
Three barriers to effective treatment for alcoholic women are described: 1) the impact of negative myths and expectancies (in particular, the myth that women do worse); 2) the impact of stereotyped sex-role expectancies which may limit and constrict women's potential for growth; and 3) the impact of the knowledge gap. The impact of each kind of barrier is elaborated as data are presented from: a clinical field experiment; a meta-analysis of a decade of research studies; and clinical experience.
Data from personal interviews and questionnaires were collected from alcoholics in treatment, alcoholism treatment agency directors and community gatekeepers. The health services utilization model proposed investigated individual predisposing factors; client attitudes and beliefs about alcohol, treatment, and health; client personal enabling traits; client social enabling characteristics; and structural characteristics of treatment services. Results discussed include the effects of structural characteristics of treatment agencies on alcoholic women's use of these agencies; gender specific differences in predisposing, personal enabling and social enabling factors and in attitudes and beliefs; ethnic differences among women in personal and environmental barriers to treatment; knowledge, attitudes and referral practices of community gatekeepers; and evaluation of workshop designed to train community gatekeepers to identify and refer alcoholics, particularly women alcoholics.
Through means of a daily diary, alcohol consumption patterns of students at a major metropolitan university were studied. Drinking displayed a weekly pattern which reflected student role demands, but was also influenced by family roles, external events, and fluctuations in academic pressures. There were distinct patterns in both percentage of students drinking and in mean ethanol consumption per drinker. There was also a clear pattern of "binge" drinking in the aftermath of stress. Drinking in the campus context was both quantitatively and qualitatively different from drinking in the family context. Chronographic analysis provides a key to understanding behavior which complements cross-sectional or longitudinal panel analysis.
Alcohol misuse has taken on epidemic proportions among some (but not all) American Indian populations. Cultural, psychological, socioeconomic and genetic etiologies have been offered to explain this social phenomenon. This study identifies the relative strengths of these causal models to differentiate among both current and lifelong drinking career patterns. Further, antecedent and drinking level differences between urban and rural Indian populations in California are described. Age, sex, level of stress as measured by the Cornell Medical Index, percent of Indian ancestry and level of drinking in the family of origin are less powerful predictors of drinking level. Policy implications of these findings include: the development of intervention programs which involve members of the patient's support network, accelerated interventions in rural Indian communities and mid-level interventions among younger and less debilitated, but identifiably "at risk", populations.
