Fast-acting antidepressant-like effects of ketamine in aged male rats

• DOI: 10.1007/s43440-024-00636-y
• Publication Date: 2024-08-19T06:40:19Z
• Authors: Elena Hernández-H...; Sandra Ledesma-Corvi; Jordi Jornet-Plaza; M. Julia García-F...
• Keywords: Male; Aging; Hippocampus* / metabolism; Prefrontal Cortex; TOR Serine-Threonine Kinases / metabolism; Prefrontal Cortex* / metabolism; Hippocampus; 0302 clinical medicine; Animals; Brain-Derived Neurotrophic Factor* / metabolism; Rats, Wistar; Antidepressive Agents* / pharmacology; Swimming; Aging* / drug effects; Cell Proliferation; Depression; Research; Brain-Derived Neurotrophic Factor; TOR Serine-Threonine Kinases; Depression / metabolism; Depression / drug therapy; Antidepressive Agents; Rats; Hippocampus* / drug effects; Cell Proliferation / drug effects; Ketamine; Prefrontal Cortex* / drug effects; Ketamine* / pharmacology

Abstract Background The aging process causes anatomical and physiological changes that predispose to the development of late-life depression while reduces efficacy classical antidepressants. Novel fast-acting antidepressants such as ketamine might be good candidates explored in context aging, especially given lack previous research on its for this age period. Thus, aim present study was characterize ketamine’s effects older rats. Methods (30 min) repeated (7 days) antidepressant-like (5 mg/kg, ip ) were evaluated 14-month-old single-housed rats through forced-swim novelty-suppressed feeding tests. In parallel, modulation neurotrophic-related proteins (i.e., mBDNF, mTOR, GSK3) assessed brain regions affected by process, prefrontal cortex hippocampus, well possible hippocampal cell proliferation. Results Acute induced a response male aged rats, observed reduced immobility test, parallel with region-specific increase mBDNF protein content cortex. However, failed induce efficacy, but decreased rate proliferation and/or other markers not modulated either paradigm ketamine. Conclusions These results complement prior data supporting effect further extend ages. Future studies are needed clarify after treatment potential adverse aging.