Changes in the postnatal development on nitric oxide system induced by serotonin depletion.

Serotonin (5-HT) is expressed early during central nervous system (CNS) development and plays an important role during this period. Nitric oxide (NO) is also involved in neuronal development. Morphological and functional relationships between NO and 5-HT, demonstrated as alterations of the nitrergic system, were observed after a 5-HT depletion. It has been hypothesized that NO may be related to the neuronal damage induced by some 5-HT neurotoxins. A parachloroamphetamine (PCA) treatment is able to damage ascending 5-HT fibers proceeding from the dorsal raphe nucleus (DRN) and depletes 5-HT storage in neuronal somata. In order to study the effects of a 5-HT depletion on the nitrergic system during postnatal development, Wistar rat pups were injected subcutaneously twice, on postnatal day (PND) 3 and PND4 with PCA. Neuronal nitric oxide synthase (nNOS) immunoreactivity and NADPH diaphorase reactivity were performed on brain sections from PND5, 7, 12, 19, 29 and 62 animals. After the treatment, we found an increased NADPH-d staining and nNOS immunoreactivity in striatum, frontal cortex and hippocampus along the different studied time periods. Interestingly, the expression of both NO markers was higher when 5-HT depletion was more evident, suggesting a very close relationship between 5-HT and NO systems during postnatal development.