Enzymatic depletion of serotonin in vivo and its consequences

The serotonin (5-HT) system in the brain is a global modulator thought to tune up a unique subset of brain keynotes such as emotion, motivation, and sleep/conscious states in the deepest seats of cognition and behavior. In pursuit for coherent accounts of such higher-order issues, we have been trying to deduce the system dynamics of 5-HT in full span from the perturbation- response couples elicited by our most quick, specific, extensive, and reversible depletion of the brain 5-HT so far available via plasma precursor annihilation by injection of a tryptophan degrading enzyme (TSO) (ISTRY meetings-1986 in Cardiff, -92 in Nagoya and -98 in Hamburg). Herein discussed are the dynamics of the 5-HT depletion both in the whole brain and regional dimensions, and then the perturbation-induced manifestation of a continuous behavioral quiescence underlain by chaotic patterns of sleep/waking states. This response in sharp contrast to those by earlier serotonin depletors, prompts us to consider a serious revision of the, current 5-HT scenario. In the light of our research, future directions will be discussed together with the RTD (rapid tryptophan depletion) claiming the impaired brain 5-HT turnover by a partial decline of plasma tryptophan.