Transcriptional Profiles in Nucleus Accumbens of Antidepressant Resistance in Chronically Stressed Mice.
bioRxiv : the preprint server for biology March 17, 2025 Trevonn Gyles, Eric M Parise, Molly S Estill et al. preprint
Treatment-resistant depression (TRD) affects about a third of patients who do not respond to standard antidepressants, yet its molecular basis is poorly understood. In a mouse model of TRD, where chronically stressed mice failed to respond to fluoxetine, subsequent ketamine treatment produced behavioral and transcriptional changes in the nucleus accumbens. Failed fluoxetine treatment primed the mice for a positive response to ketamine, and specific gene networks linked to stress susceptibility and antidepressant resistance were identified. These findings illuminate molecular mechanisms behind antidepressant resistance and address a gap in preclinical TRD models.