Integrin ?V?3 Function Influences Citalopram Immobility Behavior in the Tail Suspension Test.

ABSTRACT: Human studies first identified genetic and expression interactions between integrin ?3 and serotonin (5-HT) transporter (SERT) genes. This association has been further strengthened by our discovery that integrin ?3-containing receptors (?v?3) physically interact with, and thereby define, a subpopulation of SERTs that may represent the main target of selective serotonin reuptake inhibitors (SSRIs). In this study, we examine how integrin ?v?3 function influences the behavioral response to the highly SSRI citalopram in the tail suspension test. Mice bearing a conditional deletion of the integrin ?3 gene in neurons, or those expressing a constitutively active ?v?3 receptor, have decreased sensitivity to citalopram, when compared to wild-type littermates. To identify potential signaling pathways downstream of integrin ?v?3 that could be altered in these mouse lines, and consequently influence citalopram response in vivo, we performed antibody array analyses of midbrain synaptosomes isolated from mice bearing genetically altered integrin ?3. We then pharmacologically targeted focal adhesion (FAK) and extracellular-signal-regulated (ERK) kinases and determined that FAK and ERK activity are critical for the actions of citalopram. Taken together, our studies have revealed a complex relationship between integrin ?v?3 function, SERT-dependent 5-HT uptake, and the effective dose of citalopram in the TST, thus implicating a role for integrin signaling pathways in the behavioral response to SSRIs.

SUBMITTER: Pan H 

PROVIDER: S-EPMC6372549 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature