Time-dependent antidepressant-like effects of reelin and ketamine in the repeated-corticosterone model of chronic stress.
Kaylene K A Scheil, Carla L Sánchez-Lafuente, Brady S Reive, Ciara S Halvorson, Jennifer Floyd, Hannah M O Reid, Jenessa N Johnston, Lisa E Kalynchuk, Hector J Caruncho
Progress in Neuro-Psychopharmacology and Biological Psychiatry June 8, 2024 DOI: 10.1016/j.pnpbp.2024.110998 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 120 |
| Population | Female Long Evans rats |
| Interventions | Reelin Ketamine |
| Dose | reelin 3μg; i.v., ketamine 10 mg/kg; i.p. |
| Duration | 21-day chronic corticosterone paradigm, with behavioral and biological evaluations at 1 h, 6 h, 12 h, and 1 week after treatment |
| Topics | Depression Ketamine Esketamine |
| Keywords | Chronic stress Corticosterone Rapid-acting antidepressants Reelin Depression treatment Rapid antidepressants Brain proteins Mental health research |
| Citations | 5 |
| Key findings | Both reelin and ketamine individually reversed chronic stress-induced behavioral deficits and restored hippocampal reelin expression within one hour, with effects lasting at least one week, and their combination showed additive antidepressant-like effects at one week. |
Abstract
There is an urgent need for novel antidepressants, given that approximately 30% of those diagnosed with depression do not respond adequately to first-line treatment. Additionally, monoaminergic-based antidepressants have a substantial therapeutic time-lag, often taking months to reach full therapeutic effect. Ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist is the only current effective rapid-acting antidepressant, demonstrating efficacy within hours and lasting up to two weeks with an acute dose. Reelin, an extracellular matrix glycoprotein, has demonstrated rapid-acting antidepressant-like effects at 24 h, however the exact timescale of these effects has not been investigated. To determine the short and long-term effects of reelin, female Long Evans rats (n = 120) underwent a chronic corticosterone (CORT; or vehicle) paradigm (40 mg/kg, 21 days). On day 21, rats were treated with reelin (3μg; i.v.), ketamine (10 mg/kg; i.p.), both reelin and ketamine (same doses), or vehicle (saline). Behavioural and biological effects were then evaluated at 1 h, 6 h, 12 h, and 1 week after treatment. The 1-week cohort continued CORT injections to ensure the effect of chronic stress was not lost. Individually, both reelin and ketamine significantly rescued CORT-induced behaviour and hippocampal reelin expression at all timepoints. Ketamine rescued a decrease in dendritic maturity as induced by CORT. Synergistic effects of reelin and ketamine appeared at 1-week, suggesting a potential additive effect of the antidepressant-like actions. Taken together, this study provides further support for reelin-based therapeutics to develop rapid-acting antidepressant.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
Citations in the library
Cites 8
- Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Psychological Medicine February 12, 2016
- Pharmacological and behavioral divergence of ketamine enantiomers: implications for abuse liability Molecular Psychiatry April 15, 2021
- Ketamine Rescues Hippocampal Reelin Expression and Synaptic Markers in the Repeated-Corticosterone Chronic Stress Paradigm Frontiers in Pharmacology September 2, 2020
- Ketamine—50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms Pharmacological Reports February 20, 2021
- Reelin Rescues Behavioral, Electrophysiological, and Molecular Metrics of a Chronic Stress Phenotype in a Similar Manner to Ketamine. eNeuro August 2023
and 3 more in the library