Antidepressant‐like effect of AMPA and ketamine combination in male Wistar ‐Kyoto rats
Luli R Akinfiresoye, D. M. Lovinger, Y. Tizabi
The FASEB Journal April 1, 2012 DOI: 10.1096/fasebj.26.1_supplement.1045.9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Adult male Wistar-Kyoto (WKY) rats |
| Interventions | AMPA ketamine |
| Dose | 0.25 mg/kg, i.p. (AMPA); 0.25 mg/kg, i.p. (ketamine) |
| Duration | 10-day intervention |
| Topics | Esketamine Ketamine |
| Key points | The combination of AMPA and ketamine resulted in a significant reduction of forced swim test immobility compared to individual treatment of either AMPA or ketamine alone. |
Abstract
Studies have shown that therapeutics that act on the glutamatergic system could provide a novel mechanistic approach for the treatment of depression. We previously reported that ketamine, an NMDA antagonist, has a rapid and lasting antidepressant effect both acutely and chronically on depressive‐like behavior in Wistar‐Kyoto (WKY) rats ( Soc Neurosci Abst 2008) . Other studies had suggested that the antidepressant effect elicited by ketamine could be mediated through stimulation of AMPA receptors, we also sought to confirm this hypothesis in our animal model of depression. We discovered that AMPA by itself also has an antidepressant effects in WKY rats, both acutely and chronically ( Biol Psych Abst 2010). In this study we examined the hypothesis that the combination of AMPA and ketamine will result in either a synergistic or additive antidepressant effect when compared to the individual treatments of AMPA or ketamine alone. Adult male WKY rats were administered the combination of AMPA (0.25 mg/kg, i.p.) and ketamine (0.25 mg/kg, i.p.) for 10 days and behavior studies were done approximately 22 hr after the last injection. Controls received saline. A 5 minute forced swim test (FST), a measure of helplessness, was used to determine the drug‐induced antidepressant effects. The combination of AMPA and ketamine resulted in a significant reduction of FST immobility compared to individual treatment of either AMPA or ketamine alone. In view of the fact that an increase in AMPA/NMDA receptor function and number may be mediating the antidepressant effects of ketamine, these results suggest that a combination of AMPA and ketamine could provide an effective therapeutic treatment for depression. Supported by NIH/NIGMS (2 SO6 GM08016‐39)
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 |