Early-life treatment of antiserotonin antibodies alters sensitivity to serotonin receptors, nociceptive stimulus and serotonin metabolism in adult rats

A single systemic administration of serotonin (5-HT) antibodies on day-1 of the life of rat has been investigated for neurotransmitter contents in nucleus raphe, and several discrete brain regions, as well as for serotoninergic syndromes and nociceptive responses in adult animals. 5-HT antiserum raised in rabbits were purified and characterized prior to subcutaneous administration in neonatal rats. Control animals received normal rabbit serum. Antibodies tagged with radioactive iodine were traced in the brains of rat pups treated subcutaneously. These animals at adulthood, exhibited an increase in body weight, increased sensitivity to serotonin agonist 5-methoxy-N-N-dimethyl tryptamine, and to nociceptive stimulus to subcutaneously administered formalin. Animals neonatally treated with 5-HT antiserum once on day 1 of life, exhibited significant decrease in the contents of serotonin and its metabolite as compared to normal serum treated animals specifically in nucleus raphe dorsalis, but not in substantia gresia centralis, nucleus accumbens, nucleus caudatus putamen, substantia nigra or tuberculum olfactorium during the study period of seven days to four months. The contents of dopamine or norepinephrine were not consistently altered in any of the nuclei studied. Since 5-HT is known to act as a trophic factor for its own development and its target areas, exposure to 5-HT antibodies during birth might have adversely affected the development of the serotoninergic system and resulted in long-lasting changes in behavior and 5-HT levels in the brain. These results have strong implications for the treatment of childhood developmental disorders such as autism where hyperserotoninemia is associated with the disease syndromes.