Increased nitric oxide synthase activity in a model of serotonin depletion

Serotonin (5HT) containing cell bodies are localized in mesencephalic and r hombencephalic raphe nuclei. It has been proposed that 5HT could be involve d in neuronal development and plasticity. In the central nervous system, ni tric oxide (NO) has been postulated as a neurotransmitter and neuromodulato r, and has been implicated in neurotoxicity as well as in neuroprotection, Using the nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) technique, NO synthesizing neurons were described in raphe nuclei. By immun ohistochemistry, nitric oxide synthase (NOS) was found colocalized with 5HT in some dorsal raphe nucleus (DRN) neurons. In a model of inhibition of 5H T synthesis produced by daily administration of parachlorophenilalanine dur ing 14 days, we have studied the relationship between 5HT and NO systems af ter 5HT depletion by histochemical and immunocytochemical methods. After th e treatment, we observed an important reduction of 5HT immunostaining in th e DRN and enhanced NOS activity demonstrated by NADPH-d technique, especial ly in the dorsomedial and ventromedial subgroups. In spite of the increased NOS activity, we could not observe significant changes in the NOS-immunore activity in the DRN after 5HT depletion. These results could indicate that 5HT depletion is concomitant with changes in NOS activity without affecting NOS expression in the DRN. (C) 2001 Elsevier Science Inc.