Effect of Antibiotics on the 5‐hydroxytryptamine Content of the Small Intestine and Other Organs in Rats and Mice

Abstract

Rats and mice were given antibiotics orally and by subcutaneous injection and the effects on tissue levels of 5-hydroxytryptamine and intestinal bacteria were studied. In mice it was found that antibiotics which caused a large reduction in the bacterial flora of the intestine when given orally also caused a significant increase in intestinal 5-hydroxytryptamine. In rats, neomycin caused a reduction in the urinary excretion of 5-hydroxyindoleacetic acid. In both rats and mice, many antibiotics caused a significant reduction in the weight of the spleen.Stacey & Sullivan (1957) reported that the intestinal content of 5-hydroxytryptamine in mice was raised after oral administration of a combination of streptomycin and chlortetracycline. They found that rectal swabs from treated mice taken on the day of death were sterile, and suggested that sterilization of the gut might have increased the amount of tryptophan available for 5-hydroxytryptamine synthesis by preventing the bacterial metabolism of dietary tryptophan. The present paper reports further experiments undertaken to amplify these results. METHODSGroups of adult male mice weighing 20 to 30 g and of rats weighing 130 to 180 g were matched according to weight and age, and were litter-mates where possible. Control and treated groups received a mixed, balanced diet in cubes, and water ad lib.Antibiotics were given twice daily either orally by stomach tube or by subcutaneous injection. The doses used, roughly five times the adult human therapeutic dose in mg/kg, were as follows:(1) Neomycin, 215 mg/kg, for rats and mice. Solution for rats 50 mg/ml. and for mice 25 mg/ml. (2) Streptomycin, 70 mg/kg in a solution of 10 mg/ml. for all animals. (3) Chlortetracycline and oxytetracycline, 70 mg/kg, in a solution of 10 mg/ml. for all animals. (4) Chloramphenicol, 105 mg/kg, in a solution of 15 mg/ml. for all animals.When combinations of antibiotics were used, the same doses of the individual drugs were given. Solutions of drugs were made up, when necessary, in normal saline. Controls were given the same volume of normal saline.Animals were killed by stunning and bleeding. The whole of the spleen and brain was homogenized and aliquots taken for assay of 5-hydroxytryptamine in both rats and mice. The small intestine of mice, from the pyloric sphincter to the ileo-caecal junction, was similarly treated. The mucous membrane of the small intestine of rats was scraped off with a scalpel

Histamine and 5‐hydroxytryptamine in the Intestinal Tract of Germ‐free Animals, Animals Harbouring One Microbial Species and Conventional Animals

“…In this respect, the relatively low histamine values found in the wall of the caecum of the conventional animal, an organ where intense bacterial activity takes place, might be of significance (Tables 1 and 2). The feeding of antibiotics, which is known to give the intestinal tract a more " germfree-like " character, especially in the chicken (Gordon, Wagner & Wostmann, 1957-8;Wostmann, Wagner & Gordon, 1959-60), also increases 5-hydroxytryptamine levels (Table 3; also Sullivan, 1961). As antibiotics suppress certain flora elements (Wagner & Wostmann, 1958-9), conceivably the same organisms responsible for the flora stimulation of the intestinal tract could also cause an increase in amine oxidase activity.…”

Pathogenesis of Experimental Shock

“…However, some explanation must be provided for the large and frequent epinephrine lesions produced by SMAO shock blood from neomycinopretreated donors. Other workers have reported that the serotonin content of intestinal tissues was elevated in rats and mice receiving oral neomycin (16). In the light of this, and also because of the ability of serotonin to produce epinephrine-accelerated lesions, we became curious about the levels of serotonin in intestinal tissues of shocked rabbits previously fed neomycin.…”