Electroconvulsive therapy (ECT) remains the most effective treatment for patients with major depression, bipolar depression, mania, catatonia, and severe psychosis. Nonetheless, the mechanisms underlying the therapeutic effects of ECT largely remain unknown. While previous preclinical studies have noted a role for neurotropic signaling, neurogenesis, and alterations in monoamine neurotransmitter systems, these models were largely conducted using procedures that deviate from clinical practice. Therefore, we sought to develop a clinically relevant murine model of electroconvulsive stimulation (ECS), a model of ECT, which more closely replicates current clinical approaches and then employ this model to explore ECS mechanisms. Using the well-established chronic social defeat stress (CSDS) paradigm, known to disrupt reward and motivated behaviors, we investigated whether the behavioral changes after CSDS could be reversed following a clinically related course of ECS. Additionally, we observed induction of plasticity-related genes in the nucleus accumbens (NAcc) and amygdala, regions responsible for reward- and fear-related memory, respectively. Lastly, we investigated ECS-related changes in the NAcc with RNA-sequencing. This approach revealed a gene expression profile associated with ECS-related changes in NAcc. Pathway analysis demonstrated cellular changes primarily involved in regulating cell migration and differentiation. Therefore, utilizing our novel and clinically relevant model of ECS, we have begun to elucidate mechanisms that contribute to ECTs therapeutic outcomes by examining murine behavior and RNA from brain regions associated with stress-induced states that model anxiety and depression and the impact of ECS.