Biomedical subjects

C L Randall

Publications and source records attributed to C L Randall.

At least 55 records · Page 3Linked to original sources

PubMed1987

Stimulatory effects of ethanol in C57BL/6 mice.

Although ethanol stimulation is well documented in several species including humans, there is some controversy about whether the stimulation occurs in the highly inbred mouse strain, C57BL/6. Since inbred mouse strains are frequently used to elucidate mechanisms for individual differences in reaction to alcohol, the present study was undertaken to more completely characterize the behavioral effects of ethanol and to help resolve some of the controversy regarding the drug's stimulatory effect on C57 mice. Activity of female C57BL/6cr mice was assessed in either a lighted or dark environment for 20 min after injections of water or ethanol at doses of 0.5, 1.0, 2.0, 4.0 g/kg. Elevated activity (stimulation) was observed in mice injected with relatively low ethanol doses and tested in the light. The 2.0 g/kg dose produced a transient elevation in activity which declined rapidly across time. Animals tested under the dark condition were not stimulated by the drug but had activity reductions to high doses of ethanol. The detection of ethanol-induced stimulation appears to be related to the performance of control mice rather than a light-related difference in ethanol sensitivity.

Animals↗

PubMed1987

Central nervous system prostaglandins and ethanol.

There is growing interest in the effect of ethanol on cellular membranes, generally, and neuronal membrane systems, in particular. Perturbations of membranes have led to numerous enzymatically mediated processes, one of which is prostaglandin production. This paper reviews the nature and role of prostaglandins in the central nervous system, and what is known about the effect of ethanol on prostaglandin production in brain. Areas of central nervous system physiological function in which prostaglandins may mediate the actions of ethanol are discussed. Methodological considerations and future directions for research in the area of ethanol and prostaglandins are highlighted.

Animals↗

PubMed1987

Alcohol, pregnancy, and prostaglandins.

Basic scientists and clinicians alike are in agreement that children of alcoholic mothers are at risk for a variety of birth defects. These defects have been labeled fetal alcohol syndrome or, in a milder form, fetal alcohol effects. Prevention or therapeutic intervention of this disorder requires an understanding of the mechanism of action of alcohol on the developing fetus. This paper addresses the possible role of prostaglandins as biochemical mediators of the teratogenic actions of alcohol.

Abnormalities, Drug-Induced↗

PubMed1987

Two generations of maternal alcohol consumption in mice: effect on pregnancy outcome.

This study investigated whether female offspring of alcohol-treated mothers are, themselves, more or less susceptible than control offspring to the deleterious effects of alcohol on the outcome of their own pregnancy. One group of pregnant C57BL mice was fed a liquid diet containing 25% ethanol-derived calories (EDC) and another group was pair-fed an isocaloric (0% EDC) control diet. A third group was fed lab chow ad libitum (LC). The female offspring resulting from those matings were subsequently mated upon reaching 90 days of age. These pregnant mice were then separated into three prenatal treatments (25% EDC, 0% EDC, and LC). On gestation-day 19, second generation fetuses were removed by cesarean section, weighed, and sexed. Results indicated that number of implants, live births, and percent prenatal mortality did not differ between groups. However, fetal weight was lower in groups prenatally exposed to ethanol than in controls, regardless of the prenatal history of the mothers, themselves. More importantly, the data suggest that offspring of alcohol-treated mothers who do not consume alcohol themselves during their own pregnancy may still have a tendency to have offspring of lower birth weight. On the other hand, if mothers prenatally exposed to alcohol do consume alcohol during their own pregnancy, the impact of fetal weight suppression is even greater than expected for in utero alcohol exposure alone. These effects may be due to the fact that mothers who were prenatally exposed to alcohol weighed less than controls at the time of becoming pregnant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Alcohol as a teratogen: a decade of research in review.

The teratogenicity of ethanol has been well-documented during the past decade in clinical cases as well as animal models. It has become clear that, short of spontaneous abortion, Fetal Alcohol Syndrome represents the most serious consequence of sustained heavy drinking throughout pregnancy. The overall incidence of FAS is about 1-2/1000 live births, although it is considerably higher if one only considers alcoholic women who continue to drink during pregnancy. The incidence of Fetal Alcohol Effects (FAE) is much higher. Most clinical follow-up studies have failed to find significant improvement of intellectual functioning over time. Moreover, problems with attention, cognition, and perception have become apparent in children exposed to alcohol prenatally but without a clinical diagnosis of FAS. Animal models have demonstrated rather conclusively that ethanol is teratogenic in several species. The effect is dose-dependent and the type of malformation observed depends upon the stage of development when the exposure occurred. A single exposure in a high enough dose is sufficient to produce birth defects and decreased fetal weight in mice. Studies with rats have demonstrated behavioral defects similar to those seen clinically, including hyperactivity and deficiencies in response inhibition. Neuroanatomical reports confirm a structural defect in the hippocampus, as suggested by the behavioral deficits observed. Neurochemical correlates of impaired behavior have been inconsistent. With regard to mechanism of action, impaired placental transfer of essential nutrients has been confirmed by several laboratories, while the role of hypoxia, acetaldehyde, and prostaglandins remains to be proven conclusively. Any, or all, of these potential mechanisms may play a role in alcohol-induced teratogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Sensitivity to ethanol in female mice: effects of ovariectomy and strain.

Two experiments were conducted to investigate the influence of ovariectomy (OVX) on alcohol sensitivity in mice. In the first experiment, OVX, sham-operated, and nonsurgical control C57BL mice were examined for brain alcohol levels associated with alcohol-induced motor incoordination, alcohol-induced loss of righting reflex, and voluntary alcohol consumption. The second experiment employed four strains of mice (C57BL, C3H, DBA, and Swiss Webster) to evaluate the influence of OVX on alcohol-induced spontaneous activity. Taken together, the results indicated that surgical removal of the ovaries in mice does not influence alcohol-induced motor incoordination, loss of righting reflex, or spontaneous activity. Voluntary alcohol consumption, however, was affected by ovariectomy, since mice in the OVX group consumed less alcohol relative to body weight (g/kg) than controls.

Alcohol Drinking↗

PubMed1985

Effects of ethyl alcohol on human peripheral lymphocytes.

Chronic alcoholics are more susceptible to infection and have increased incidences of certain types of carcinomas. One explanation for this may be suppressed immune responses secondary to ethyl alcohol consumption. This project was initiated to study the effect of ethyl alcohol on lymphocyte responses in vitro by monitoring tritiated thymidine uptake. Lymphocytes were incubated in the presence of phytohemagglutinin-P, concanavalin A, and pokeweed mitogen. The response of normal lymphocytes was noted after mitogen stimulation in the presence of ethyl alcohol in graded doses. Ethyl alcohol levels greater than or equal to 50 mg/dL suppressed tritiated thymidine uptake of normal lymphocytes for phytohemagglutinin-P and concanavalin A. Since ethyl alcohol exposure in concentrations consistent with blood levels that may be attained during routine ingestion significantly decreased lymphocyte blastogenesis, it is speculated that chronic ethyl alcohol ingestion may alter immune surveillance sufficiently to be responsible in part for the increased incidence of infection and/or neoplasms seen in alcoholic subjects.

Adult↗

PubMed1984

Adrenalectomy reduces alcohol-stimulated activity: blood and brain alcohol content.

It has been shown that adrenal glucocorticoids have a permissive role in some of the actions of alcohol. To determine if an intact adrenal was necessary for the stimulation of locomotor activity, 24 female C3H mice were tested for open field activity with ethanol or saline. Two weeks after adrenalectomy or sham surgery, animals were tested for activity again with ethanol or saline. One week later, alcohol disappearance curves were generated for blood and brain. Adrenalectomy reduced but did not abolish the alcohol-stimulated locomotor activity. In addition, adrenalectomy significantly reduced estimated peak alcohol levels in blood and brain but significantly reduced the disappearance rate for alcohol only in brain. These data suggest that adrenalectomy significantly changes alcohol distribution, with greater impact on brain alcohol levels than on blood levels, and that this may be responsible, at least in part, for the reduction in stimulated locomotor activity.

Adrenalectomy↗

PubMed1983

In vivo regional levels of PGE and thromboxane in mouse brain: effect of decapitation, focused microwave fixation, and indomethacin.

A focused microwave fixation technique was tested for use in determining basal PGE and thromboxane B2 levels of mouse brain. Focused microwave irradiation (3.5 Kw/0.4 sec) to the head of C3H mice produced basal values of PGE and TXB2 which were five-fold less than those in animals killed by decapitation. Indomethacin (10 mg/kg) pretreatment blocked the decapitation rise in PGE and TXB2 levels and gave values similar to focused microwave irradiation. Indomethacin pretreatment combined with microwave fixation did not reduce PG levels more than microwave treatment alone. When microwave fixation was used, there was no difference in regional (cerebral cortex, whole cerebellum, midbrain, hypothalamus) levels of either PGE or TXB2. However, PGE levels were significantly higher than TXB2 in all regions. After decapitation there was a greater increase in TXB2 than PGE. The cerebellum produced less PGE and TXB2 after decapitation compared to the other regions. Our results confirm the usefulness of the focused microwave irradiation technique for examining in vivo basal prostaglandin levels in mouse brain.

Animals↗

PubMed1983

Effect of prenatal alcohol exposure on consumption of alcohol and alcohol-induced sleep time in mice.

An animal model was used to examine the effect of maternal alcohol administration on behaviors in the offspring which might predispose to alcoholism. Pregnant C3H mice were administered a liquid diet containing 28% ethanol-derived calories (EDC) from Gestation-Day 8 until parturition. Control animals were either pair-fed an isocaloric 0% EDC diet or received standard lab chow and water throughout pregnancy. Offspring were tested for sleep time following a challenge dose of 3.5 or 4.5 g/kg ethanol at 25 or 110 days of age or for consumption of 10% w/v ethanol in a two-bottle choice situation. The results demonstrated that prenatal exposure to alcohol did not affect alcohol-induced sleep time at either testing age or dose and that waking blood alcohol levels were similar across groups. Voluntary alcohol consumption, however, was higher in mice exposed to alcohol in utero during the initial week of testing but intake decreased to near control levels by the third week. Whether other alcohol-related behaviors are altered by prenatal alcohol exposure remains to be examined.

Alcohol Drinking↗

PubMed1983

Acute alcohol intoxication, mood states and alcohol metabolism in women and men.

The course of alcohol absorption and elimination was investigated in seven women and nine men administered a moderate (0.66 ml/kg) dose of 95% ethanol. Women were tested during the postmenstrual phase (Day 6-7), when levels of estrogen and progesterone were estimated to be relatively low. Data reflecting alterations in physical sensations, perceived levels of intoxication, and positive and negative mood states were also collected. Women reached significantly higher peak blood alcohol concentrations (BAC's) than men (p less than 0.01). However, differences in peak BAC's between men and women could be explained by differences in body water content between the sexes. When the raw data on BAC's were corrected for differences in body water content between men and women, no difference in the amount of alcohol metabolized, or in the length of time necessary to metabolize that amount of alcohol, could be found between the sexes. Although women attained higher blood and, presumably, brain levels of ethanol, men did not differ from women in perceived levels of intoxication, physical sensations and mood states. Acute alcohol intoxication appeared to elevate positive mood states during the ascending limb of the BAC curve, but was associated with increased negative affect during the descending limb.

Adult↗

PubMed1983

Amoxapine elevates serum prolactin in depressed men.

It has been suggested that the antidepressant amoxapine might have neuroleptic properties. Clinically, an increase in serum prolactin occurs during neuroleptic treatment secondary to post-synaptic dopamine blockade. Ten men who met DSM-III criteria for major depression exhibited a significant increase in their serum prolactin over drug-free baseline values during treatment with amoxapine. A comparison group of 12 depressed men treated with desipramine showed no such increase. Combined with that of others, our study suggests that amoxapine might have antipsychotic properties and, therefore, be useful in treating conditions where a combined antidepressant and neuroleptic effect is required.

Amoxapine↗

PubMed1983

Alcohol use, negative mood states, and menstrual cycle phases.

This study investigated the hypothesis that alcohol consumption patterns among normally menstrually cycling women would be influenced by increased negative mood states and phase of the menstrual cycle. A time-series, within-groups design was used to allow for comparisons among normally cycling women, women maintained on oral contraceptives, and men. Thirty-two adults recorded daily estimates of ongoing behaviors in the areas mentioned for two menstrual cycles or equivalent periods. Radioimmunoassay and temperature data were used to confirm ovulation and to define ovulatory, premenstrual, and menstrual phases. Estimates of anxiety, depression, and hostility were highly intercorrelated, but negative moods were not significantly related to frequency/amount of alcohol consumption. However, normally cycling women reported significantly more negative moods, were frequent drinking to relieve tension/depression, and more frequent solitary drinking at menstruation. These relationships were not observed among oral contraceptive women or men. Collected among psychologically robust, working subjects of high intelligence, these data provide estimates of baseline functioning for future studies exploring the progression of pathological alcohol use patterns among women.

Adult↗

PubMed1983

Inhibition of prostaglandin synthesis by indomethacin does not affect alcohol consumption in inbred mice.

The prostaglandin system has been implicated in mediating both the acute and chronic pharmacologic effects of alcohol. The effect of blockade of prostaglandin synthesis by indomethacin on genetically based alcohol preference in C57BL/6, C3H/He, and BALB/c mice was examined. Although strain typical alcohol preference patterns were observed, there was no effect of indomethacin on either naive or preestablished alcohol preference and consumption. Genetically transmitted alcohol preference may be a complex system in which prostaglandin synthesis does not play a part.

Alcohol Drinking↗

PubMed1982

Acute alcohol intoxication, negative affect, and autonomic arousal in women and men.

The present study tested the hypothesis that acute moderate alcohol intoxication is associated with reductions in experimentally-induced negative affect among 64 moderately drinking adult women and men. The effort incorporated a balanced placebo design, multiple measures of affective responses including cardiovascular and electrodermal activity, and control for phase of the sexual cycle among nonoral contraceptive women. Negative effect and psychophysiological responses to intoxication following stress manipulation were a complex function of beverage, expectancy, and gender. Expectation of a moderate alcohol dose among women at the premenstruum was associated with higher levels of self-reported anxiety, whereas alcohol consumption guised as tonic seemed to be related to tension reduction. Alcohol tended to increase autonomic arousal among men, but there were no significant changes in negative affect. Moderate intoxication was associated with increased heart rate regardless of gender, and alcohol expectancy increased levels of skin conductance for men and women.

Adult↗

PubMed1982

The effect of paternal alcohol consumption on fetal development in mice.

The purpose of this study was to evaluate the effect of chronic paternal alcohol consumption on fetal growth and development in C3H mice. Male mice were pair-fed isocaloric liquid diets containing either 30%, 20%, or 0% ethanol-derived calories, or given free access to lab chow. After four weeks of treatment, all males were allowed to mate with untreated females. No differences were found between the litters of alcohol-treated males and controls in terms of the number of implantation sites, prenatal mortality, fetal weight, sex ratio, or frequency of soft tissue malformations. The results suggest that paternal alcohol consumption does not grossly alter fetal growth and development in C3H mice.

Abnormalities, Drug-Induced↗

PubMed1981

Alcohol sensitivity in female mice: effect of ovariectomy.

This study tested the hypothesis that decreased estrogen levels accomplished by removing the ovaries affect the response to acutely administered alcohol in female mice. Sensitivity to alcohol was measured in ovariectomized, sham-operated, and non-surgical control C3H/HEN mice. Each animal received an IP injection of alcohol (3.0 or 4.0 g/kg). Core temperature, fall time, sleep time, and waking blood alcohol levels were the dependent variables. For each of these measures, alcohol sensitivity was found to be a function of the dose of alcohol administered, but not the surgical condition. Additionally, the stage of estrus in control animals was not found to be related to alcohol sensitivity.

Animals↗

PubMed1981

Prenatal alcohol exposure: current issues and the status of animal research.

Animal studies of the tetratogenicity of alcohol have proliferated during the past few years. The purpose of this state-of-the-art is to overview some of the issues that the researchers have studied, to address methodological problems inherent in studies in this area, and to suggest directions for future research.

Abnormalities, Drug-Induced↗