Dose-related effects of prenatal 5-methoxytryptamine (5-MT) on development of serotonin terminal density and behavior.

Our previous studies with a tissue culture model of neuronal development have shown that the development of serotonin neurons is dependent, at least in part, on the stimulation of high affinity serotonin receptors. One receptor inhibits the outgrowth of neurons, while the other promotes it. The present study was therefore undertaken to replicate these findings in a whole animal model system. Pregnant Sprague-Dawley rats were treated from gestational day 12 until birth with 0.1, 1.0 or 3.0 mg/kg 5-methoxytryptamine (5-MT). The pups were assessed for serotonin outgrowth by the selective synaptosomal uptake of [3H]serotonin at postnatal days 1, 15 and 30 (D1, D15, D30). In addition, the pups were tested behaviorally for the neonatal serotonin syndrome at D5 (induced by quipazine), spontaneous alternation and open field activity at day 15 and lick suppression at day 30. At 1.0 mg/kg, the terminal outgrowth of serotonin neurons was inhibited, while the highest dose, 3.0 mg/kg, showed stimulation of outgrowth. The highest dose caused behavioral alterations which had abated by 30 days, while the intermediate dose (1.0 mg/kg) showed behavioral changes throughout. Interestingly, the lowest dose, 0.1 mg/kg, showed changes in uptake only at D1 and behavioral changes only at later timepoints, principally at D30. This suggests that serotonin not only plays a role in regulating the development of the neurons which produce it, but that it may also play a role in neurochemical imprinting--that is, changes in behavior in the adult may be due to changes in neurochemistry during development, even though that neurochemistry may have been corrected by the time the animal becomes an adult.