Evaluation of sigma (σ) receptors in the antidepressant-like effects of ketamine in vitro and in vivo.
Matthew J Robson, Meenal Elliott, Michael J Seminerio, Rae R Matsumoto
European Neuropsychopharmacology April 2012 DOI: 10.1016/j.euroneuro.2011.08.002 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical laboratory study Peer reviewed |
|---|---|
| Population | PC12 cells and rodents in the forced swim test |
| Interventions | Ketamine NE-100 BD1047 NGF |
| Measures | Competition binding assays, neurite outgrowth in PC12 cells, forced swim test |
| Topics | Esketamine Ketamine |
| Key points | Ketamine bound to sigma-1 and sigma-2 receptors with micromolar affinity and potentiated NGF-induced neurite outgrowth in PC12 cells, an effect attenuated by the sigma antagonist NE-100. However, ketamine's antidepressant-like effects in the forced swim test were not attenuated by the sigma antagonists NE-100 or BD1047. The authors suggest sigma receptor-mediated neuronal remodeling may contribute to ketamine's antidepressant effects. |
Abstract
Ketamine is an NMDA antagonist and dissociative anesthetic that has been shown to display rapid acting and prolonged antidepressant activity in small-scale human clinical trials. Ketamine also binds to σ receptors, which are believed to be protein targets for a potential new class of antidepressant medications. The purpose of this study was to determine the involvement of σ receptors in the antidepressant-like actions of ketamine. Competition binding assays were performed to assess the affinity of ketamine for σ(1) and σ(2) receptors. The antidepressant-like effects of ketamine were assessed in vitro using a neurite outgrowth model and PC12 cells, and in vivo using the forced swim test. The σ receptor antagonists, NE-100 and BD1047, were evaluated in conjunction with ketamine in these assays to determine the involvement of σ receptors in the antidepressant-like effects of ketamine. Ketamine bound to both σ(1) and σ(2) receptors with μM affinities. Additionally, ketamine potentiated NGF-induced neurite outgrowth in PC12 cells and this effect was attenuated in the presence of NE-100. Ketamine also displayed antidepressant-like effects in the forced swim test; however, these effects were not attenuated by pretreatment with NE-100 or BD1047. Taken together, these data suggest that σ receptor-mediated neuronal remodeling may contribute to the antidepressant effects of ketamine.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 28
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Legal highs: staying on top of the flood of novel psychoactive substances Therapeutic Advances in Psychopharmacology January 26, 2015
- From “Special K” to “Special M”: The Evolution of the Recreational Use of Ketamine and Methoxetamine CNS Neuroscience & Therapeutics June 1, 2013
and 23 more in the library
Cites 18
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder The Journal of Clinical Psychiatry July 13, 2010
- Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil. Synapse August 1, 2009
and 13 more in the library