Antidepressant-like effect of low dose ketamine and scopolamine co-treatment in mice.
Tracey L Petryshen, Michael Lewis, Kelly A Dennehy, Jacob C Garza, Maurizio Fava
Neuroscience Letters May 4, 2016 DOI: 10.1016/j.neulet.2016.03.051 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Ketamine Scopolamine |
| Dose | ketamine 3 mg/kg intraperitoneal (i.p.); scopolamine 0.1 mg/kg i.p. |
| Measures | forced swim test (FST) |
| Topics | Depression Esketamine Ketamine |
| Keywords | Acetylcholine Behavior Mouse Muscarinic Nmda |
| Key points | Co-administration of otherwise subeffective doses of ketamine (3 mg/kg) and scopolamine (0.1 mg/kg) reduced immobility time in the mouse forced swim test by 45% compared with vehicle controls, whereas either drug alone had no effect. The authors suggest this combination may be efficacious for depression and warrants human clinical trials. |
Abstract
Current medications for depression typically require weeks of treatment before significant clinical improvement is observed, and are only effective in a relatively small subset of patients. Recent human clinical studies have demonstrated that ketamine, an NMDA receptor antagonist, and scopolamine, a muscarinic acetylcholine receptor antagonist, produce rapid antidepressant responses within hours of administration, and are effective in treatment-resistant patients. We hypothesize that efficacy and tolerability may be improved by combining lower doses of both drugs in the treatment of depression. We therefore conducted a preclinical study in mice to assess whether co-treatment of low doses of scopolamine and ketamine that alone are ineffective has antidepressant-like effects in the forced swim test (FST), an assay with predictive validity for antidepressant drugs. Whereas single administration of ketamine (3mg/kg intraperitoneal [i.p.]) or scopolamine (0.1mg/kg i.p.) did not reduce immobility time in the FST, co-administration of both drugs at these doses significantly reduced immobility time by 45% compared to vehicle treated controls. These results suggest that the combination of subeffective doses of ketamine and scopolamine may prove efficacious for the treatment of depression and should be evaluated in human clinical trials.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
Citations in the library
Cited by 3
- Phencyclidine and Scopolamine for Modeling Amnesia in Rodents: Direct Comparison with the Use of Barnes Maze Test and Contextual Fear Conditioning Test in Mice Neurotoxicity Research April 21, 2018
- Ketamine-induced antidepressant like effects in mice: A possible involvement of cannabinoid system. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie April 1, 2019
- Do psychoactive drugs have a therapeutic role in compulsivity? Studies on schedule-induced polydipsia. Psychopharmacology February 2018
Cites 8
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- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology January 2012
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and 3 more in the library