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Nonetheless, the mechanisms underlying its therapeutic effects 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 ECT, referred to as electroconvulsive stimulation (ECS) in animals, which more closely aligns with current clinical approaches to better explore its mechanisms. Using the well-established chronic social defeat stress (CSDS) paradigm, known to negatively impact reward processes, 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 bulk RNA-sequencing. Pathway analysis demonstrated cellular changes primarily involved in neuroplasticity and regulating cell migration and differentiation. Therefore, utilizing our novel and clinically relevant model of ECS, we have begun to elucidate mechanisms that contribute to ECT\u2019s therapeutic outcomes by examining murine behavior and RNA from brain regions associated with stress-induced states that model anxiety and depression and the effects of ECS.<\/jats:p>","DOI":"10.1101\/2025.02.12.637719","type":"posted-content","created":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T00:05:23Z","timestamp":1739577923000},"source":"Crossref","is-referenced-by-count":0,"title":["A Clinically Aligned Murine Model of Electroconvulsive Stimulation Reverses Social Aversion and Displays Fear Memory Impairment After Chronic Social Defeat Stress"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9583-6956","authenticated-orcid":false,"given":"Michael D.","family":"Kritzer","sequence":"first","affiliation":[{"name":"Neurobiology of Fear Laboratory, Basic Neuroscience Division, McLean Hospital, Belmont, MA, USA"},{"name":"Division of Neuropsychiatry and Neuromodulation, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie A.","family":"Maddox","sequence":"additional","affiliation":[{"name":"Neurobiology of Fear Laboratory, Basic Neuroscience Division, McLean Hospital, Belmont, MA, USA"},{"name":"Department of Psychology and Human Development, SUNY Empire State University, Saratoga Springs, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle X.","family":"Chen","sequence":"additional","affiliation":[{"name":"Neurobiology of Fear Laboratory, Basic Neuroscience Division, McLean Hospital, Belmont, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu","family":"Dan","sequence":"additional","affiliation":[{"name":"Klengel Lab, McLean Hospital, Belmont, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"Herbert E.","family":"Covington","sequence":"additional","affiliation":[{"name":"Department of Psychology and Human Development, SUNY Empire State University, Saratoga Springs, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Miczek","sequence":"additional","affiliation":[{"name":"Tufts University, Department of Psychology, Medford, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan A.","family":"Camprodon","sequence":"additional","affiliation":[{"name":"Division of Neuropsychiatry and Neuromodulation, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torsten","family":"Klengel","sequence":"additional","affiliation":[{"name":"Klengel Lab, McLean Hospital, Belmont, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerry J.","family":"Ressler","sequence":"additional","affiliation":[{"name":"Neurobiology of Fear Laboratory, Basic Neuroscience Division, McLean Hospital, Belmont, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041110000681000_2025.02.12.637719v1.1","doi-asserted-by":"crossref","unstructured":"Abe R, O. 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