OBJECTIVETo investigate whether 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) treatment alters the morphology of serotonin (5‐HT) fibers in the in the dorsal (DRN) and median raphe nuclei (MRN) where 5‐HT cell bodies are located.DESIGN AND METHODSMale C57BL/6J mice were treated with 4 doses of MPTP 20 mg/kg (i.p.) at every 2 hours and sacrificed after 3 and 16 weeks. Tryptophan hydroxylase (TPH) antibody was used for immunohistochemistry to study the neuronal number and fiber lengths and tail suspension test (TST) to assess depression‐like behavior of the mice.RESULTSIncreased expression of TPH in the cell bodies and fibers of MPTP treated mice, were noticed without any significant differences in the neuronal number in the DRN and MRN at both 3 and 16 weeks survival times, as compared to control group. However, a significant decrease in fiber lengths in DRN and MRN at 3weeks survival period and in MRN at 16 weeks survival period after MPTP treatment, were observed. The consistent reduction in fiber lengths in the MRN correlated well with our earlier report in MPTP treated mice with preferential decrease in the density of thick beaded 5‐HT axons in the PFC which originate from MRN. Increased immobility as measured by the TST was observed in the MPTP treated mice.CONCLUSIONMPTP treated mouse may be a useful resource to model depression associated with PD. Supported by NIH SNRP/NINDS grant NS041071.