Summer Research Description: The serotonin transporter (SERT) is important for regulation of the serotonin system, which has been implicated in multiple neuropsychiatric disorders. Integrin αVβ3 has been shown to interact in a protein complex with SERT and to modulate SERT activity via integrin αVβ3 engagement. Integrin αVβ3 engagement activates focal adhesion kinase (FAK), which initiates a signaling pathway that leads to activation of mitogen/extracellular signal-regulated kinase (MEK) and its down-stream targets. The purpose of this project is to determine whether targeting FAK and MEK pathways by selective inhibitors in vivo is sufficient to induce changes in SERT function and, consequently, behavioral responses in mice. We will evaluate changes in the serotonin system using the tail suspension test (TST), a behavioral test that is sensitive to acute administration of selective serotonin reuptake inhibitors. We will determine whether in vivo administration of FAK or MEK inhibitors elicits a significant reduction in immobility time in the TST. We will then measure serotonin reuptake in the mouse midbrain to verify that this behavioral response results from changes in SERT function. These studies will reveal the pharmacological potential of targeting integrin signaling pathways for the modulation of the serotonin system in vivo.