Distinct Molecular Responses to Ketamine and Imipramine in Cortical and Striatal Regions Following Acute Swim Stress
Biomolecules March 24, 2026 Veronica Begni, Floriana de Cillis, Natascha Pfeiffer et al.
Classical and rapid-acting antidepressants alter how the brain responds to acute stress through different molecular programs. In mice exposed to swim stress, imipramine dampened stress-induced neural activation in the cortex and striatum, while ketamine preserved it. Hippocampal activation remained robust and unaffected by either drug. BDNF expression changed only in the striatum, where imipramine reduced the stress-related increase. Both drugs similarly promoted active coping behaviors, but through distinct mechanisms. The findings suggest that cortical and striatal transcriptional signatures differentiate classical from rapid-acting antidepressant action, though human studies are needed to confirm clinical relevance.