Ketamine reverses chronic stress-induced behavioral changes via Ca2+-permeable AMPA receptors in mice
Joshua C. Flowers, Paige E. Vetter, McKennon J. Wiles, Seung Hyun Roh, Ellison R. Black, Evelina Bouckova, Madison H. Wustrau, Rahmi Lee, Sang-Hun Lee, Seonil Kim
bioRxiv Preprint Server October 7, 2024 preprint DOI: 10.1101/2024.10.07.616991 via bioRxiv
Summary
AI-generated from the abstractChronic stress disrupts AMPA receptor signaling in the hippocampus, contributing to anxiety, depression, and cognitive decline. Low-dose ketamine rapidly increases GluA1-containing, GluA2-lacking calcium-permeable AMPA receptors (CP-AMPARs) in hippocampal neurons, enhancing glutamatergic synaptic strength and reducing anxiety- and depression-like behaviors in naïve animals. Ketamine may also protect against chronic stress effects, but whether CP-AMPARs mediate its antistress actions remains unknown.
Study at a glance
| Characteristics | Review |
|---|---|
| Intervention | Ketamine |
| Dose | low-dose |
| Keywords | Stress studies Stress science Stress investigation Stress findings Chronic stress research |
| Citations | 2 |
| Key finding | The role of CP-AMPARs in ketamine's antistress effects is largely unknown. |
Abstract
Background and Purpose Chronic stress affects brain functions leading to the development of mental disorders like anxiety and depression, as well as cognitive decline and social dysfunction. Among many biological changes in chronically stressed brains, disruptions in AMPA Receptor (AMPAR)-mediated synaptic transmission in the hippocampus are associated with stress responses. We have revealed that low-dose ketamine rapidly induces the expression of GluA1-containing, GluA2-lacking Ca2+-Permeable AMPARs (CP-AMPARs), which enhances glutamatergic synaptic strength in hippocampal neurons. Additionally, subanesthetic low-dose ketamine decreases anxiety-and depression-like behaviors in naïve animals. In addition to reducing depression, some research indicates that ketamine may have protective effects against chronic stress in both humans and animals. However, the role of CP-AMPARs in the actions of ketamine’s antistress effects is largely unknown.