Biomedical subjects

M Sarviharju

Publications and source records attributed to M Sarviharju.

12 recordsLinked to original sources

PubMed1994

Effects of lifelong ethanol consumption on the ultrastructure and lipopigmentation of rat heart.

The myocardial interactions of ageing and lifelong ethanol ingestion were studied in the ethanol-preferring AA (Alko Alcohol) line of rats. Samples of the left ventricle from young control rats (3-month), old control rats (30-month) and rats exposed to ethanol from 3 to 30 months of age, were studied in terms of myocardial ultrastructure and lipopigmentation. Electron microscopic morphometry showed an age-related increase in the volumetric densities of lipofuscin and unspecified sarcoplasm, while the proportions of mitochondria, myofibrils and tubular structures remained unaltered in the left ventricular myocardium. Lifelong ethanol exposure increased the proportion of sarcoplasmic reticulum and transverse tubules, apparently due to dilation of the tubular structures. Mitochondria were significantly larger in the ethanol-exposed rats compared to the control rats of the same age, while the volumetric proportion of mitochondria tended to decrease in the ethanol-exposed group. Fluorescence microscopic image analysis showed that myocardial lipopigmentation (proportion of myocardial area covered by autofluorescent lipopigments) was about two-fold in the old ethanol-exposed rats compared to the old control rats, and 13-fold compared to the young controls. It is concluded that ageing and chronic ethanol ingestion produce rather different patterns of alteration in myocardial ultrastructure, which does not support the concept of ethanol-induced accelerated ageing. The enhancement of myocardial lipofuscin accumulation is thought to reflect chronic oxidative stress in the hearts exposed to ethanol.

Age Factors↗

PubMed1992

Interaction of aging and lifelong ethanol ingestion on ethanol-related behaviors and longevity.

The interactions of aging and long-term voluntary ethanol consumption were studied in the alcohol-preferring AA (Alko Alcohol) rats. The mean daily ethanol intake was 6.45 +/- 0.31 g/kg/day (mean +/- SE) at the beginning of the exposure at 3 months of age. The control animals were given only food and water ad libitum. There was no difference in survival or weight gain between the control and ethanol groups. When tested for voluntary ethanol intake at the age of 24 months, the rats in the ethanol group consumed significantly more ethanol than the controls. The two groups did not differ in ethanol-induced motor impairment, sleep-time, or hypothermia, nor in the rate of ethanol elimination. The 24-month-old animals, however, showed higher sensitivity to ethanol than the 3-4-month-old rats in the sleep-time test. It is concluded that the feeding regimen used in this study did not produce any detectable interactions between ethanol and the aging processes in the AA rats.

Aging↗

PubMed1987

Alcohol-preferring (AA) and alcohol-avoiding (ANA) lines of rats after introgression of alien genes.

Outcrossing has been used as a method for introducing new genetic variability into the high-drinking AA and low-drinking ANA rat lines that had reached their selection limits and were suffering of poor fertility and decreased litter size. The response to the renewed selection for differential alcohol consumption, and the effect of outcrossing upon the components of productivity are reported.

Alcohol Drinking↗

PubMed1986

Enzymes of catecholamine metabolism in the brains of rat strains differing in their preference for or tolerance of ethanol.

The activities of the catecholamine-synthesizing and inactivating enzymes were determined in whole brains of two pairs of rat strains differing in their genetically-determined behavioural responses to ethanol. The alcohol-tolerant (AT) rats did not show any significant differences in enzyme activities when compared with the non-tolerant (ANT) strain. The activity of tyrosine hydroxylase was found to be significantly higher in brains of the alcohol-preferring (AA) rats, than in those of the alcohol-non-preferring (ANA) strain.

Animals↗

PubMed1983

Alcoholic neuropathy and hepatopathy in mice. An experimental study.

Seventeen young adult C57BL male mice were given 15% (w/v) solution of ethanol as their sole drinking fluid for seven to nine months. C57BL male mice given regular drinking water were used as controls. After decapitation samples from the livers and the sciatic nerves of the mice were processed for electron microscopy and morphometry. The ultrastructural analysis revealed slight alterations in the nerves of the ethanol-exposed mice. The changes were mostly in the Schwann cells. Pathological Schwann cell-axon relationships were also more abundant in the ethanol-exposed mice. The thickness distribution of the myelinated nerve fibers was similar in the exposed and the control mice. The transverse-sectional area of hepatocytes was greater in the mice on ethanol than in the controls. The volume density of lipid vacuoles of the liver cells was significantly increased in the mice treated with ethanol (p less than 0.001). The hepatic changes indicate a significant effect of ethanol on the liver. The findings suggest that, in mice, chronic peroral treatment with ethanol can produce slight changes suggesting peripheral neuropathy together with fatty metamorphosis of the liver.

Alcoholism↗

PubMedDate not supplied

Motor impairment, narcosis and hypothermia by ethanol: separate genetic mechanisms.

The AT and ANT rat lines, developed by selective outbreeding for differential ethanol-induced motor impairment, were tested for their sensitivity to the hypothermic and narcotic (loss of righting reflex) effects of ethanol. In contrast to the large differences between the lines in their degree of motor impairment, as measured with both the tilting-plane and rotarod tests, only minor differences were observed in duration of loss of righting reflex or hypothermia. Therefore, we suggest that genetically determined factors influencing motor impairment are for the most part dissociated from the factors determining the hypothermic and narcotic effects of ethanol.

Alcoholic Intoxication↗

PubMedDate not supplied

Revitalization of the AA and ANA rat lines: effects on some line characteristics.

After 37 generations, the AA and ANA rat lines developed for high and low voluntary alcohol consumption, were revitalized by crossing with hybrid (Brown Norwegian X Lewis) rats. The line difference in alcohol consumption continued, although initially diminished, after revitalization. The greater acetaldehyde accumulation and longer loss of righting reflex after ethanol administration of the ANAs persisted after revitalization, but significant line differences in motor impairment were no longer found. The line characteristics for open-field test behavior were also different than before revitalization. Of the previously-observed line differences that have now been reexamined, the level of blood acetaldehyde during ethanol metabolism appears to be the most closely related to the genetically-determined factors influencing alcohol consumption.

Acetaldehyde↗

PubMedDate not supplied

A simple procedure using 4-methylpyrazole for developing tolerance and other chronic alcohol effects.

Young rats given ethanol chronically by gradually increasing the concentration in the drinking fluid to 17.5% reached a maximal daily consumption of 15-17 g ethanol/kg body wt., which corresponded to 35-40% of their energy intake. This chronic treatment was markedly potentiated by additional supplementation of the drinking fluid with a low dose of the alcohol dehydrogenase inhibitor 4-methylpyrazole. Rats on this regimen exhibited higher and more sustained blood ethanol levels. Consequently, more pronounced functional and metabolic tolerance developed and more frequent signs of physical dependence was observed than in rats drinking only ethanol solution. Simple provision of drinking fluid supplemented with ethanol and 4-methylpyrazole appears to provide a nutritionally adequate and easy way to produce tolerance and other chronic alcohol effects.

Animals↗

PubMedDate not supplied

Cerebellar GABAA receptors in two rat lines selected for high and low sensitivity to moderate alcohol doses: pharmacological and genetic studies.

Alcohol-sensitive (ANT) rat line produced by selective outbreeding for high acute sensitivity to the motor-impairing effects of ethanol, displays unusual cerebellar GABAA receptor pharmacology. The ANT rats have enhanced benzodiazepine agonist affinity at their binding sites for an imidazobenzodiazepine, [3H]Ro 15-4513, normally not affected by agonists at all, and reduced GABAA agonist, [3H]muscimol, binding, when compared to the alcohol-insensitive (AT) rat line. In the present study, the benzodiazepine receptor difference was localized to the cerebellar granule cell layer. This receptor difference was not found in ex vivo binding studies after lorazepam administration, although brain lorazepam concentrations in both rat lines similarly exceeded 1 microM. An indication for differential binding in vivo between the lines was, however, observed, as pretreatment with lorazepam accentuated the relative accumulation of radioactivity only in the cerebellum of the AT rat line after an intravenous injection of a trace amount of [3H]Ro 15-4513, thus revealing benzodiazepine insensitivity for a portion of the cerebellar [3H]Ro 15-4513 binding in the AT but not in the ANT rats. In the second generation of AT/ANT cross-breeding, there was no clear association of alcohol sensitivity and cerebellar receptor binding. There was, however, a significant positive correlation between the [3H]muscimol binding and the diazepam-insensitive [3H]Ro 15-4513 binding in the cerebellum. In conclusion, the receptor defect in the cerebellar granular cell layer of the alcohol-sensitive ANT rats was also detectable in vivo, but it may not explain the enhanced alcohol sensitivity of these rats.

Animals↗

PubMedDate not supplied

Ethanol sensitivity and consumption in F2 hybrid crosses of ANT and AT rats.

ANT rats that are highly sensitive to the motor-impairing effects of moderate ethanol doses voluntarily drink less ethanol in a free-choice test between 10% (v/v) ethanol solution and water than the ethanol-insensitive AT rats, suggesting the possibility that ethanol drinking is affected by initial ethanol sensitivity. However, in the F2 hybrid crosses of ANT and AT rats, voluntary ethanol drinking did not correlate with sensitivity to the motor-impairing effects of ethanol in the tilting plane test. Therefore, initial ethanol sensitivity does not appear to be a major factor in explaining variation in voluntary ethanol drinking.

Alcohol Drinking↗

PubMedDate not supplied

Phenotypic characterization of second generation offspring of alcohol-sensitive ANT and alcohol-insensitive AT rat lines.

The alcohol-sensitive ANT and the alcohol-insensitive AT rat lines developed by selective breeding for differential sensitivity to motor impairment on the tilting plane by a moderate ethanol dose (2 g/kg, IP), were cross-bred to produce second generation (F2) offspring to study phenotypic correlations between various behavioral and biochemical properties and the degree of initial alcohol sensitivity in the tilting plane test. The F2 population (n = 75) was subjected to alcohol sensitivity tests using a tilting plane test and a sleep time test, and to the elevated plus-maze test of sober activity and anxiety. Finally, the animals were sacrificed and the concentrations of dopamine and its acidic metabolites were analyzed in their striatal tissues. Serum corticosterone was determined to obtain information about the stress responses of the animals after the tilting plane test. The behaviors studied had no significant correlations with each other, suggesting that the various genetic and environmental factors affecting these behavioral phenotypes are different for each behavior. The biochemical measures yielded some correlations with the tilting plane test results that were contrary to the differences between the parent rat lines (dopaminergic indices) or that were confounded by the correlations with the body weight of the animals (corticosterone). Body-weight independent correlational tendency between the alcohol-induced impairment in motor performance and serum corticosterone concentration, however, fitted the differences between the parent lines, suggesting that stress mechanisms cannot be fully excluded as factors contributing to the differential alcohol sensitivity between the ANT and AT rat lines.

Animals↗

PubMedDate not supplied

Tolerance for the decrease in nerve conduction velocity and for the motor impairment produced by ethanol in mice: differential development during chronic ethanol consumption.

C57BL/6J/BOM mice were given 15% (w/v) ethanol solution as their sole drinking fluid. Nerve conduction velocities (NCV) and motor coordination (ataxia) of the unanesthetized animals were examined after a single IP injection of 3.0 g ethanol/kg body weight at 6, and 9 months after the start of drinking and after 3 months of abstinence. During chronic consumption of ethanol, tolerance for relative conduction time (RCT) change developed in six months. This tolerance was not observed after 9 months of ethanol treatment. The tolerance for ataxia persisted throughout the period of ethanol treatment. After a three month's abstinence, no differences between the controls and the animals previously on ethanol were observed regarding responses to acute ethanol administration. These observations suggest that different mechanisms underlie the development of tolerance for the effect of ethanol on peripheral nerve conductance and for the ataxia from ethanol in the central nervous system.

Alcoholism↗