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We have previously demonstrated an augmentation of serotonergic activity within various brain areas following infusion of brain‐derived neurotrophic factor (BDNF) into the midbrain near the periaqueductal gray and dorsal and median raphe nuclei (PAG/DR). However, the mechanism of this BDNF‐induced modulatory effect on serotonergic systems was unclear. The aim of the present work was to study the regulation of tryptophan hydroxylase (TPH) mRNA levels after chronic BDNF administration invivo. TPH mRNA levels were measured using a quantitative competitive reverse transcription polymerase chain reaction (RT‐PCR) assay. A significant increase in the expression of TPH mRNA (13‐fold) was found within the PAG/DR as early as 24 hr after onset of BDNF infusion and was sustained throughout the duration of infusion (11 days). This was accompanied by increased serotonin (5‐hydroxytryptamine, 5‐HT …