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Biomedical subjects

G E McClearn

Publications and source records attributed to G E McClearn.

At least 109 records · Page 6Linked to original sources
PubMed1981

Genetic influences on alcohol consumption and actions of alcohol.

Recent studies, utilizing twin pairs and adoption paradymes, have demonstrated hereditary influences on alcohol drinking behavior and on the risk of alcoholism. It is well recognized that alcoholism is a complex condition involving a number of actions of alcohol and alcohol related behaviors. It is not surprising, therefore, that investigations, in man, have demonstrated individual differences in ethanol metabolism and other actions of alcohol and that these individual differences appear to be genetically influenced as well as influenced by environmental factors. Numerous studies have been conducted over the past decade which demonstrate, in animals, a genetic influence on alcohol metabolism and on the actions of alcohol. In this review, the evidence for a genetic influence on central nervous system sensitivity to the effects of alcohol have been discussed including studies with inbred strains of mice and selectively bred lines of mice and rats. The review summarizes studies which suggest a genetic influence on the acquisition of both acute and chronic tolerance to ethanol and upon the display of withdrawal symptoms following the discontinuance of chronic ethanol exposure. It is clear that heredity has ubiquitous influence on alcohol related processes and that these genetic influences are expressed at the behavioral, pharmacological and neurochemical levels.

Alcohol Oxidoreductases↗
PubMed1980

Fertility, maternal care, and offspring behavior in mice prenatally treated with tobacco smoke.

Female mice from lines selectively bred for differences in open-field activity were exposed to tobacco smoke during gestation. Smoke-treated females were less likely than controls to have produced litters by 23 days after observation of a vaginal plug. Within the high-active line, fewer pups of smoke-treated dams survived to weaning. Regardless of treatment, fewer high-active than low-active offspring survived to weaning. Results of a 4-day series of open-field activity tests administered to offspring beginning at 28 days of age indicated that tobacco smoke administered prenatally and/or during testing depresses open-field activity in both lines. Other activity tests administered at 50 days of age gave similar results. Tissue nicotine levels after nicotine injection tended to be higher in high-active and control groups than in low-active and smoke-treated groups, respectively. Liver weight expressed as percentage of body weight was 11.9% greater in smoke-treated animals than in controls.

Animals↗
PubMed1980

Interrelationships of alcohol consumption, actions of alcohol, and biochemical traits.

Voluntary alcohol consumption, acute tolerance, and central nervous system (CNS) sensitivity to ethanol are potentially informative measures concerning human alcoholism. Little is understood regarding the associations among these parameters or between these traits and neurochemical processes such as brain protein or brain enzyme activities. A powerful strategy is to assess a large number of characteristics simultaneously on all individuals as a heterogeneous sample. This permits rapid screening of a large number of variables with respect to their interrelationships. Identification can thus be made of those variables that are elements of the caudal nexus, and subsequent experimental research can attack the problem of identifying mechanisms. The present study employed mice from the HS/Ibg stock which is maintained by systematic random mating to assure genetic heterogeneity. The results demonstrate that voluntary ethanol consumption and acquisition of acute tolerance to ethanol were positively associated, whereas these measures were not significantly related to CNS sensitivity to ethanol. In addition, ethanol preference was inversely related to soluble brain protein. The activities of the soluble enzymes from brain, aldehyde reductase and glucose-6-phosphate dehydrogenase, were not significantly associated with ethanol preference, acquisition of acute tolerance, or CNS sensitivity to ethanol. Unexpectedly, more than 30 percent of the variance in voluntary alcohol consumption could have been predicted from the measurements of acquisition of acute tolerance, and vice versa.

Alcohol Drinking↗
PubMed1979

Ethanol consumption and hepatic enzyme activity.

Enzyme activity and ethanol consumption were measured in an F2 generation derived from the C57BL and C3H inbred mouse strains. A significant correlation (0.25) was found between alcohol dehydrogenase activity and ethanol acceptance in the F2 generation. Mass selection from a genetically heterogenous mouse stock, HS/Ibg, has yielded high ethanol acceptance (HEA) and low ethanol acceptance (LEA) lines of mice. The mean ethanol acceptance scores for the fifth generation of these lines are 1.008 and 0.606, respectively. The total liver alcohol dehydrogenase activity was found to be 24% higher in the HEA line than in the LEA line after five generations of selective breeding. No association between cytosolic aldehyde dehydrogenase activity and ethanol acceptance was found in either the F2 generation or the fifth generation of the selectively bred lines.

Alcohol Drinking↗
PubMed1979

Influence of genetic variables on means, variances, and covariances in behavioral responses to toxicological and pharmacological substances.

Inbred strains and F1 generations provide strong experimental control in toxicological studies by virtue of the relative stability of their means. Their variances do not always conform to simple expectations, with respect either to each other or to segregating populations. For the evaluation of covariances or correlations, populations of choice are genetically segregating ones. A genetic approach of demonstrated power but as yet limited application to toxicological problems is that of selective breeding, a procedure by which lines of animals can be developed to precise specifications.

Analysis of Variance↗
PubMed1978

The influence of brain damage on locomotor behavior of mice selectively bred for high or low activity in the open field.

Locomotor activity was measured in mice with lesions restricted to the neocortex, in animals with hippocampal damage, and in sham-operated control mice of the selectively bred high and low open-field activity lines developed by J. C. DeFries. Postoperatively, the high-activity animals with hippocampal lesions showed reduced activity relative to those with only neocortical damage, and their postoperative activity levels were uncorrelated with those obtained preoperatively. Testing the animals under reduced illumination enhanced locomotor activity, with the greatest increase demonstrated by high-activity mice with hippocampal damage. While increases in activity under low illumination did occur in the low-activity line, no significant group differences were observed. Amphetamine did not affect locomotor behavior of the high-activity control animals, whereas doses of 1.0 and 10.0 mg/kg reduced the activity of the low-activity mice. High-activity mice with hippocampal damage evidenced a significant increase in locomotor behavior after the 10.0 mg/kg dose. These results emphasize that the behavioral effects of brain lesions and pharmacological manipulations cannot be adequately assessed without regard to genotype of the animals under investigation.

Amphetamine↗
PubMed1978

Activating and anesthetic effects of general depressants.

The long-sleep (LS) and short-sleep (SS) lines of mice were derived by selective breeding with respect to ethanol sleep time. We found that in current generations LS mice also have longer sleep times than SS mice to trichloroethanol and paraldehyde. Two subsequent experiments tested our hypothesis that mice that are relatively insensitive to the hypnotic effects of depressant drugs might be relatively activated by low doses of these drugs. Both experiments failed to support the hypothesis. First, although SS mice were more activated than LS mice by subhypnotic doses of paraldehyde, the lines did not differ in the degree of activation produced by low doses of trichloroethanol. Second, among mice from a genetically heterogeneous population (HS), there was no relation between the degree of activation induced by a low dose of ethanol and sensitivity to the hypnotic effects of a higher dose.

Animals↗
PubMed1978

Parent-offspring resemblance for specific cognitive abilities in Korea.

Regressions of offspring on midparent value for tests of specific cognitive abilities in Korea were considerably higher than those for Americans of Japanese ancestry or Americans of European ancestry tested in Hawaii. This greater parent-offspring resemblance in Korea may be due to the particular method of test administration or to an increased genetic variance resulting from assortative mating. The pattern of parent-child correlations for three relatively pure tests of spatial ability and for the spatial factor did not conform to that of a sex-linked recessive character.

Adolescent↗
PubMed1978

Ethnic variation in use and effects of alcohol.

Americans living in Hawaii were questioned about their use of alcoholic beverages. Although alcohol use was widespread in all ethnic groups included in the study, comparisons among groups showed that (a) a larger proportion of Orientals than Caucasians reported no use of alcohol, (b) Caucasians reported heavier use, and (c) a larger proportion of Oriental users reported facial flushing as a sequel to alcohol consumption. Persons with one Oriental and one Caucasian parent were intermediate with respect to (a) and (b), but were more similar to Orientals on (c). Other symptomology reported appeared to be associated with amount imbibed, not with ethnicity per se. Compared to current users, former users reported a larger number of problems and symptoms associated with alcohol use.

Adult↗
PubMed1976

Effect of hypnotics on mice genetically selected for sensitivity to ethanol.

It was previously shown that the rate of disappearance of blood ethanol was identical for two lines of mice selectively bred for differences in sleep-time after ethanol administration. The ED50 values for the loss of righting response with ethanol were significantly different at 3.64 g per kg for the SS line and 1.65 g per kg for the LS line. In the present study the mean sleep time is 367 sec for SS mice and 9342 sec for LS mice. The ED50 values remain essentially the same as previously reported. Unchanged LD50 values for ethanol, however, are not different at 4.8 g per kg for the SS and 4.5 g per kg for the LS line of mice. The ED50 value for loss for righting response following administration of methanol, butanol and t-butanol is approximately 2 fold greater for the SS line of mice than for the LS line. The ED50 values for sodium pentobarbital or ether in the 2 lines of mice for loss of righting response are virtually identical. In addition, the sleep-time values obtained after the administration of pentobarbital, chloral hydrate, trichloroethanol and paraldehyde are not significantly different. These data indicate that while the SS and LS lines of mice differ in central nervous system sensitivity to ethanol, methanol, butanol and t-butanol it is implied that they do no differ in central nervous system sensitivity to other hypnotic agents tested. Proof of this latter suggestion awaits determination of metabolic rates, and brain levels of these other depressants.

Animals↗