5-Hydroxytryptophan uptake and decarboxylating neurons in the cat hypothalamus

Parachlorophenylalanine, an inhibitor of tryptophan hydroxylase, induced a virtually total disappearance of serotonin-immunoreactivity in the hypothalamus of the cat. After intrahypothalamic injection of 5-hydroxytryptophan, an immediate precursor of serotonin in cats pretreated with parachlorophenylalanine, serotonin-immunoreactivity was detected in many fibers surrounding the injection site. Furthermore, when 5-hydroxytryptophan was injected with inhibitor of monoamine oxidase, a large number of small neurons immunoreactive to serotonin was identified in many discrete regions: the anterior and lateral hypothalamic areas, preoptic area, suprachiasmatic nucleus, dorsal hypothalamic area, dorsomedial nucleus, posterior hypothalamic area and nucleus of the fields of Forel. Serotonin-immunoreactivity was also evident in the thick axon bundles in the lateral hypothalamus. The distribution pattern of these cells was quite similar to that of aromatic L-amino acid decarboxylase, which catalyses the conversion of 5-hydroxytryptophan to serotonin and that of L-3,4-dihydroxyphenylalanine to dopamine. However, we failed to demonstrate serotonin-immunoreactivity in these parvocellular neurons without monoamine oxidase inhibitor. It is possible that 5-hydroxytryptophan is decarboxylated to serotonin by aromatic L-amino acid decarboxylase but rapidly degraded by monoamine oxidase-A, the enzyme which preferentially deaminates serotonin. In contrast, serotonin-immunostaining was always demonstrable after intrahypothalamic injection of 5-hydroxytryptophan without monoamine oxidase inhibitor in magnocellular neurons located in the ventrolateral posterior hypothalamus and which contain exclusively monoamine oxidase-B and histidine decarboxylase. It appears that in these cells and axons, serotonin, possibly formed by histidine decarboxylase, is not rapidly oxidized by monoamine oxidase-B. Possible roles of serotonin as a neurohormone in sleep-waking regulation and of trace amines in the brain are discussed.