Serotoninergic development in the postnatal rat brain.
Various characteristics of the developing serotoninergic system in the brain of rats aged 1 to 28 days were studied biochemically. The levels of the precursor amino acid tryptophan showed a maximal increase in the blood, brain and cerebrospinal fluid (CSF) during the 7th and 10th postnatal days. The development of tryptophan hydroxlyase activity measured in vivo by means of 5-hydroxytryptophan (5-HTP) accumulation after NSD 1015 was closely related to the 5-hydroxytryptamine (5-HT) levels at the various ages. 5-HTP accumulation and 5-HT levels increased most markedly after the second postnatal week. 5-Hydroxyindoleacetic acid (5-HIAA) levels were found to increase rapidly in the brain but somewhat more slowly in the CSF during the second week of postnatal development. Regional studies of 5-HTP accumulation after NSD 1015, 5-HT and 5-HIAA levels indicated a caudal to rostral way of maturation. The disappearance of 5-HT was measured after inhibition of tryptophan hydroxylase with H 22/54. The half-life generally decreased in the various brain parts with advancing age, and in the younger animals the shortest half-life was found in the most caudal brain parts. At 28 days of age the half-life was similar in all brain parts studied. These results indicate the existence of an adult like nerve impulse flow in the 5-HT neurons in the brain stem region of the newborn rats. The results from this investigation clearly indicate that th maturation of the different biochemical parameters of the 5-HT pathways develop in a caudal to rostral direction. The study also supports the view that tryptophan hydroxylase may be the limiting step in the development of the serotoninergic system.
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000502:physiology; D001592:Benzyl Alcohols / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002997:Clomipramine / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism
D001592:Benzyl Alcohols; D006834:Hydrazines; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; C004297:3-hydroxybenzylhydrazine; D006916:5-Hydroxytryptophan; D001142:Aromatic-L-Amino-Acid Decarboxylases; D002997:Clomipramine; D011339:Probenecid