Relation of sex and ageing to serotonin metabolism in rats.

The present study deals with serotonin (5-HT) metabolism at the central and peripheral levels in young, middle-aged and old male and female rats. From middle age, the level of endogenous 5-HT and the uptake of [14C] 5-HT were higher in the platelets of female rats than in those of male rats. By contrast, the retention of [14C] 5-HT by the platelets of male rats decreased after middle age. The 5-hydroxyindoleacetic acid (5-HIAA) level in plasma was lower in males than in females, and this level increased significantly with age in males. In brain, the tryptophan level decreased significantly with age in male rats, while the 5-HT level increased in males as well as females. The brain 5-HIAA level increased significantly with age in male rats. These results confirm that 5-HT metabolism is modified during the ageing process in rats, and that several factors may be involved in this modification.

Aging and intraspecific interactions in acute hypoxic survival of specific pathogen free OF1 mice of both sexes.

In light-synchronized pathogen-free OF1 mice, and LD50 acute hypoxic challenge was performed during the light period in which respiratory and motor activities are minimal. In males and females acute hypoxic resistance decreases with age. Grouping by ten significantly decreases hypoxic survival in young, adult, and senescent males, and in young females. In young mice, hypoxic survival is significantly less in males than in females, whether or not they have interindividual contacts. This sex-related difference disappears with aging in separated individuals, but remains in 230- and 420-day-old mice when there are interindividual contacts.

Recent advances in investigations of toxicity of automotive exhaust.

The influence of auto exhaust on man's health is difficult to gauge considering the intricacy of human environmental urban stresses and particularly of other air polluting (industrial, domestic) emissions. Epidemiological surveys made in road tunnel employees and in traffic officers have not demonstrated specific effects and have often been complicated by cigarette smoking as a factor. Long-term animal experiments run mostly on small rodents give evidence of little effect of the pathological actions of dilutions such as those encountered in high polluted cities. However the acute toxicity of gasoline exhaust emission is well known and mostly due to carbon monoxide. Considering the different types of cycles and operating conditions of vehicles (gasoline and diesel), auto exhaust gases constitute no more a chemical entity than they show, a definite toxicity. A great number of substances that they contain (nitrogen oxides, aldehydes, antiknock additives, heavy metals, possible catalysts are highly toxic as shown by in vivo and in vitro (mutagenic) tests. Interactions of the components are for the moment ignored or poorly understood. Besides, the evolution of the physicochemical properties and natures of the auto exhaust emission in the gaseous biotope of man under determined conditions of ultraviolet irradiation, temperature, and hygrometry provoke the formation of secondary products such as oxidants and ozone. Several experiments show clearly that irradiation increases the toxicity of auto exhaust significantly. For these reasons, geographical, meteorological, and chronological (circadian and seasonal) factors should be taken into consideration, especially with regard to emission standards.

Action of psychoactive drugs on sex-related differences of OF1 mice; intraspecific aggressiveness and acute hypoxia survival.

The purpose of this study was to examine (1) whether there were a relationship between the sex-related differences in 51-day-old OF1 mice, regarding male aggressiveness and their sensitivity to an acute hypoxic (nitrogen) 50% lethal challenge, and (2) whether these sex-related differences could be modified by psychoactive drugs acutely injected at nonincapacitating doses. The introduction of a previously isolated male in grouped (10) mice decreased survival to the hypoxic challenge more in females than in males. The previously isolated male, which acted as an 'aggressor' with grouped mice (fights and flights in male groups, and mounts in female groups), had a higher hypoxic mortality than the mice of the groups under aggression. Psychoactive drugs were intraperitoneally injected in grouped mice before the introduction of the male aggressor. Clorazepate (5 and 25 mg/kg) abolished the sex-related difference in hypoxic survival in groups in the presence of, but not in the absence of, the previously isolated male. Conversely, hydroxyzine (5 mg/kg) and dexamphetamine (1 mg/kg) suppressed the sex-related difference only in the absence of the aggressor. The effects of these drugs appeared to be associated more with flight than with fight reactions provoked by the introduction of the male aggressor. A deep hypothermia was noted in clorazepate-treated mice at the issue of the hypoxic challenge.

Respiratory behavior in groups of deaf and non-deaf GFF male mice.

Carbon dioxide emission (VCO2) of groups of 10 GFF mice, genetically deaf and non-deaf, were compared, in controlled conditions of temperature 20-21 degrees C, humidity 50-80% and light (LD12:12; L = 108 lux). A circadian rhythm of VCO2 was evidenced in both genotypes, with levels in D and in L significantly (0.001 less than p less than 0.01) greater in deaf than in non-deaf mice. Photic VCO2 variations were significantly (0.001 less than p less than 0.05) smaller at L----D and D----L in the deaf than in non-deaf genotype. Ultradian (tau greater than 20 minutes) rhythms were evidenced in both genotypes; Fourier periodic analysis showed several significant (0.001 less than p less than 0.05) differences between these 2 genotypes concerning mainly amplitudes, whilst spectral analysis showed slight frequency differences between them. Survival to an acute nitrogen hypoxia or to an acute carbon monoxide intoxication which was significantly (p less than 0.001 and p less than 0.05) lower in deaf than in non-deaf individuals confirms the differences in respiratory behavior of groups of these two strains of mice.

Starvation and respiratory rhythmic behavior in groups of light-dark synchronized Sprague-Dawley rats.

Twenty adult male SPF Sprague-Dawley rats, grouped by 5 and synchronized by a light (L)-dark (D) 12:12 alternation, were deprived of food and water for 7 days; 20 other rats were taken as controls. Continuous measurement of emitted carbon dioxide (VCO2), which was taken as an index of respiratory and metabolic exchanges, shows that starvation significantly (p less than 0.001) decreases the amplitudes of the circadian VCO2 rhythms (by 42.5% during L and 35.6% during D) and also the L----D photic VCO2 responses (by 9.2%; p less than 0.05). Concerning ultradian rhythms of mean and great periods (40 min less than tau less than 24 hr), food and water suppression diminishes their amplitudes (by 58.4% in L and 32.4% in D) and changes their phases (by a 1.29 radian advance in L and a 0.68 radian delay in D). Rats recovered their prestarvation circadian and ultradian VCO2 rhythms 6-7 days after food and water had been given back to them.

Environmental pollution: the experimental and the human approach.

Thirty years have elapsed since laws preventing large scale pollution have begun to be made and enforced in industrial countries. Due partly to economic considerations, the actual methodology for the evaluation of health risks is now beginning to be considered. If the routine experimental and epidemiological investigations are complementary, their use, which needs respective delays of 4-5 and 20-30 years, is not adopted to determine the health effects of new chemicals or novel energies. To make up for these deficiencies, especially concerning the screening of carcinogenic and mutagenic potentials of chemicals, short in vitro tests have been developed, but they have not yet proved to be reliable. Among several investigational needs, the psychophysiological aspects of environmental pollution and the long-term effects of several kinds of nonionizing radiations, which more and more invade our environment, ought to be considered.

Effects of B16 melanoma transplantation on the respiration of grouped C57Bl female mice.

Two batches of 110 females C57Bl mice were grafted with B 16 melanoma, the first batch at the age of 67 days, the second at 82 days. The animals were divided into groups of 10, and kept under a LD 12 : 12 regimen. The growth of the tumors was more rapid in the second batch. This was accompanied in this batch, by a decrease in body growth, a diminution of heart rate and an increase in QRSII amplitude. Significant decreases in carbon dioxide emission (VCO2) level, mostly during the dark period of time, when the mice had their greatest activity, and decrease in respiratory photic variations at light transitions were obtained when the tumors were well developed. Harmonic analysis of the continuous recording of carbon dioxide shows slight changes in VCO2 ultradian (40 minutes less than tau less than 12 hours) rhythms. The effects on respiration were confirmed by different survival rates and rectal temperatures between tumor grafted and controls submitted to an acute nitrogen normobaric hypoxia.

Lead, cadmium, iron, zinc, copper, manganese, calcium and magnesium in SPF male rats exposed to a dilution of automotive exhaust gas throughout their lives.

Male pathogen free CFE albino Sprague Dawley rats were exposed 8 h per day, 5 days per week, for three years to a 1/1000 dilution of automotive exhaust gas, containing 58 ppm carbon monoxide, 0.37% carbon dioxide, 23 ppm nitrogen oxides, 2 ppm aldehydes, less than 5 mg/l hydrocarbons and 8.5 micrograms/m3 lead. Lead, cadmium, iron, zinc, calcium and magnesium were measured by atomic absorption in the femurs and tibias of the rats which died during the experiment. A comparison with two control groups revealed that the only significant difference in the elements measured in the bones was a 500% increase in lead concentration. The calculations of the correlations between the percentages of the elements in bones, the ages and the body weights of the rats, as well as cluster analysis, did not show consistent variations of the water, calcium, magnesium concentrations nor of the other studied metals related to this increase in lead concentration. Moreover, longevity was the same in the 3 groups of rats, but the body weight was statistically smaller (4%) in the group exposed to the auto exhaust dilution.

Age and survival of an acute carbon monoxide intoxication: an animal model.

Pathogen-free OF1 male and female mice of six different ages (between 31 and 387 days), grouped by 10, sex-separated and synchronized by a light (100 lux)-dark 12:12 alternation, were submitted to an acute LD50 carbon monoxide intoxication during the light period during which respiratory and motor activities are at a minimum. For this range of ages carbon monoxide survival is not significantly influenced by age and is significantly (P less than 0.001) less so in males than in females. Resistance to the acute carbon monoxide challenge seems more related to factors influencing the longevity of this mouse strain where grouped males are particularly aggressive than to respiratory exchanges (VCO2), heart frequencies or body temperature.

Sex-related factors in acute carbon monoxide intoxication in one strain of mice.

In the OF1 mouse strain, males are less resistant than females to acute carbon monoxide intoxication. Castration of males increases their resistance to carbon monoxide. For Neonates injected with four different doses of testosterone (20-500 mg per kg) or oestradiol (2-50 mg per kg), more effect on resistance to carbon monoxide in the (adult) mice was found for oestradiol than for testosterone. Pregnancy decreases resistance to carbon monoxide intoxication. Experiments performed with males and females of different ages, in various societal conditions, show the effects of sex-related dimorphism and aggressiveness. The sex-related difference in carbon monoxide resistance is not modified by a previous hypoxic stress (nitrogen hypoxia, carbon monoxide intoxication, sodium cyanide injection) but is suppressed when the CO intoxication is carried out at a low ambient temperature (13 degrees C).

Hypoxia survival variations in male and female mice as functions of chronological and environmental factors.

The inhalation by mice for 20 min of 5.5% oxygen in nitrogen, performed 29 times over 40 months, causes a mortality of 49.81%. Correlation coefficients were calculated between hypoxia mortality and different parameters: environmental--lighting, temperature, hygrometry, barometric pressure, biological--sex, age, body weight; and chronological--circadian, circannual, pluriannual. Partial correlation coefficients eliminate several interrelationships and finally point out the statistical significance of transfer from dark to light (p less than 0.001), of circadian (p less than 0.05), and of circannual (p less than 0.01) hypoxic mortality variations. Moreover, a significant (p less than 0.001) sex-related difference of mortality (males: 56.94%; females : 41.14%) was observed, independently of the environmental and chronological parameters studied.

Biological parameters in Japanese quail genetically selected for resistance or sensitivity to an acute hypoxic survival.

Various biological parameters were measured in two strains of Japanese quail selected for their resistance (Ls+) or susceptibility (Ls-) to an acute normobaric hypoxic challenge. Adults of these two strains showed very little or no significant differences concerning body weights, carbon dioxide emission, photoperiodic (L----D and D----L) respiratory reactions, cloacal temperatures, heart rates and ECG QRSII amplitudes, red blood cell data, hemoglobin electrophoresis, and plasma corticosterone (before and after an hypoxic challenge). Enzymatic capacities of phosphofructo-and pyruvate kinases, of glucose-6-phosphatase, lactico- and malate-dehydrogenases, measured in brains and hearts, showed but few statistically significant differences. Changing societal contacts did not suppress the differences of acute hypoxic survival between the two strains. Several statistically significant differences which concern reproduction and eggs, and especially egg laying and egg water vapor conductance were noted between the two strains.

Sex-related factors in acute hypoxia survival in one strain of mice.

In mice of different ages from the OF1 mouse strain, males are less resistant than females to a normobaric hypoxia obtained in a few hours by a progressive lowering of normoxic PO2 with nitrogen flushing. Injection of estradiol to castrated males and spayed females increases hypoxic survival. Neonates which have been injected with a high dose of estradiol show, when adult, a high hypoxic resistance. In adult females, hypoxic survival is lower during diestrus than during estrus. Pregnancy decreases resistance to hypoxia. Experiments, performed with males and females of different ages, show the effects of sex-related dimorphism and aggressiveness. Hypoxias at various ambient temperatures demonstrate that the sex difference in hypoxic survival persists in spite of variations in rectal temperatures.

Evidence of genetic differences in acute hypoxia survival.

In a population of Japanese quail, a genetic selection was performed leading to two strains--one resistant and one susceptible to an acute hypoxic nitrogen challenge as well as to an acute carbon monoxide intoxication. Crossing these two strains gives an F1 hybrid whose survival to acute hypoxia appears to be very close to the susceptible strain. The difference in acute hypoxic survival already appears in embryos at the age of 12 d. Susceptibility to acute hypoxia seems to be a dominant character.