A small group of neurons in the hypothalamic dorsomedial nucleus (DMN) have been reported to contain serotonin after pharmacological treatments enhancing brain serotonin levels. This study aimed at elucidating whether these neurons are able to synthesize serotonin de novo, and whether they possess a specific serotonin transport mechanism. Serotonin content in these neurons was raised by administration of l-tryptophan and pargyline. Double immunostaining for serotonin and tryptophan hydroxylase (TpOH), the serotonin synthesizing enzyme, revealed that none of the serotonin-containing neuronal somata expressed TpOH. Intracerebro-
ventricular colchicine treatment did not result in TpOH-IR in these neurons. Fluoxetine, a specific serotonin transport inhibitor, prevented the accumulation of serotonin in these neurons. The present results thus indicate that the serotonin-containing DMN neurons are not able to synthesize serotonin. Instead, they take up exogenous serotonin via a specific serotonin transport mechanism. As serotonin and DMN are associated with various physiological functions, such as regulation of food intake and modulation of fear and anxiety, the mechanisms revealed in the present study may participate in these clinically important brain functions.