Effect of neonatal hypothyroidism on the serotonin system of the rat brain

The effects of neonatal thyroidectomy and thyroid hormone replacement therapy on the development of serotonin-containing neurons in discrete rat brain nuclei were studied. Newborn male rats were rendered hypothyroid by the injection of 125 mu Ci 131I, and, after 45 days, were compared with normal littermate controls and 131I-injected animals subsequently maintained by daily T4 injections. The serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) contents of discrete brain nuclei removed by punches of frozen brain slices were measured by HPLC with electrochemical detection. 5-HT and 5-HIAA contents were significantly increased in many nuclei of the hypothyroid rat brain. By blocking the biosynthesis of 5-HT with p-chlorophenylalanine we found that the activity of tryptophan hydroxylase is an important step in the stimulatory effect of hypothyroidism on the 5-HT and 5-HIAA contents. Furthermore, we demonstrated after blockage of monoamine oxidase activity with pargyline, a less pronounced decline of 5-HIAA in neonatal hypothyroid animals, thus causing a relative accumulation of this metabolite. These results demonstrate that there are important modifications of the 5-HT system in the brain of neonatal hypothyroid rats. This may have an important role in the development of hypothyroid-induced impairments of central nervous system function.