Rody Kingston


Summer Research Description: Different antidepressants often target common serotonergic and dopaminergic systems. However, antidepressants are not 100% effective suggesting that there are still multiple cellular mechanisms contributing to depression. Antidepressant responses by novel compounds are typically identified in preclinical models using the Tail Suspension Test (TST), a behavioral stress model that measures immobility time after exposure to an inescapable environment. The TST can predict chronic antidepressant efficacy after acute administration, where effective antidepressants decrease immobility time. Although the predictive validity of the TST is well established, the cellular mechanisms underlying the antidepressant-driven immobility responses remain unknown. The purpose of this study is to identify the central nervous system cellular pathways that respond to the TST. Three antidepressants will be used in this study: modafinil, which targets the dopaminergic system; olanzapine, and citalopram, which target the GABA and serotonin systems, respectively. Common pathways mediating the immobility effects of these antidepressants will be identified by immunohistological analysis using phosphorylated extracellular signal-related kinases as markers of neuronal activity. The implications of this study include the identification of cellular pathways activated by acute antidepressant treatment, and the minimum cellular pathways that are necessary for efficacious therapeutic effects, facilitating the synthesis of compounds that properly combat depression.