Polymorphisms in the gene, FKBP5, and its resulting protein, FKBP51, are associated with stress-related disorders. Although FKBP51 inhibitors may have antidepressant-like effects, the relevant brain regions mediating this effect are still unknown. We found that FKBP51 expression is elevated in serotonin neurons of the mouse dorsal raphe nucleus (DRN) after stress, so we tested whether FKBP51 inhibition in the DRN by the novel FKBP51 antagonist, SAFit2, has antidepressant-like effects. First, we implanted guide cannulas into the DRN of wildtype mice stereotaxically, then we habituated the mice to 2.5% sucrose-containing bottles in their home cages overnight. On the following two days, the mice were stressed through repeated forced swims after receiving either SAFit2 (n=8) or a vehicle (n=7) to the DRN via the cannulas, prior to each swim session. That evening, the mice underwent a sucrose preference test to assess motivation by quantifying sucrose versus water preference using lickometers. On the next day, the mice were tested in a three-chambered social interaction test, where one chamber contained a wired cup enclosing another mouse of the same sex and the other chamber had an empty wired cup. Our results show that the SAFit2 and vehicle mice had the same immobility time during the forced swim stress, signifying that SAFit2 did not interfere with our immediate stressor. The SAFit2 mice demonstrated an increased preference for sucrose after stress compared to the vehicle mice, indicating greater motivation to consume a pleasurable liquid. However, there was no significant difference in the time spent interacting with the same sex during the social interaction test. This suggests that SAFit2 may have blocked stress-induced anhedonia by inhibiting FKBP51 activity in serotonergic neurons, as measured by the sucrose preference test. Further studies of FKBP51 inhibition in the DRN can lead to potential therapeutic treatments of neuropsychiatric disorders.