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

Male Aging Hippocampus* / metabolism Prefrontal Cortex TOR Serine-Threonine Kinases / metabolism Prefrontal Cortex* / metabolism Hippocampus 03 medical and health sciences 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
DOI: 10.1007/s43440-024-00636-y Publication Date: 2024-08-19T06:40:19Z
ABSTRACT
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.
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