Nitric oxide transforms serotonin into an inactive form and this affects neuromodulation

Nitric oxide is a highly reactive molecule, diffusible and therefore ubiqui tous in the central nervous system. Consequently, nitric oxide or nitric ox ide-derived nitrogen oxides must enter into contact with neuromodulators an d they can modify these molecules, especially monoamines, and thus change t heir regulatory action on synaptic transmission. We tested this possibility on a well-known, identified cholinergic synapse of Aplysia buccal ganglion , in which we have found that evoked acetylcholine release was decreased by extracellularly applied serotonin. We show that this modulatory effect of serotonin was largely reduced not only in the presence of 3-morpholinosydno nimine, a nitric oxide donor, but also when endogenous nitric oxide synthas e was activated. We have shown that this decrease in the serotonin effect i s due to the formation of chemical derivatives of serotonin, mainly a symme tric serotonin dimer, 4-nitroso-serotonin and 4-nitro-serotonin, which are ineffective in reproducing the modulatory effect of serotonin. Serotonin is involved in the regulation of several central functions, such as sleep-wak e activity or mood. The consequences of chemical modifications of serotonin by nitric oxide mus t be taken into account in physiological as well as pathological situations . In addition, our results highlight the importance of the physiological im plications of interactions between free radicals and neuromediators in the nervous system. (C) 1999 IBRO. Published by Elsevier Science Ltd.