Luli Akinfiresoye1, Yousef Tizabi. 1. Department of Pharmacology, Howard University College of Medicine, 520 W Street NW, Washington, DC, 20059, USA.
Abstract
RATIONALE: A number of preclinical and clinical studies suggest that ketamine, a glutamate N-methyl-D-aspartate receptor antagonist, has a rapid and lasting antidepressant effect when administered either acutely or chronically. It has been postulated that this effect is due to stimulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. OBJECTIVE: In this study, we tested whether AMPA alone has an antidepressant effect and if the combination of AMPA and ketamine provides added benefit in Wistar-Kyoto rats, a putative animal model of depression. RESULTS: Chronic AMPA treatment resulted in a dose-dependent antidepressant effect in both the forced swim test and sucrose preference test. Moreover, chronic administration (10-11 days) of combinations of AMPA and ketamine, at doses that were ineffective on their own, resulted in a significant antidepressant effect. The behavioral effects were associated with increases in hippocampal brain-derived neurotrophic factor, synapsin, and mammalian target of rapamycin. CONCLUSION: These findings are the first to provide evidence for an antidepressant effect of AMPA and suggest the usefulness of AMPA-ketamine combination in treatment of depression. Furthermore, these effects appear to be associated with increases in markers of hippocampal neurogenesis and synaptogenesis, suggesting a mechanism of their action.
RATIONALE: A number of preclinical and clinical studies suggest that ketamine, a glutamateN-methyl-D-aspartate receptor antagonist, has a rapid and lasting antidepressant effect when administered either acutely or chronically. It has been postulated that this effect is due to stimulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. OBJECTIVE: In this study, we tested whether AMPA alone has an antidepressant effect and if the combination of AMPA and ketamine provides added benefit in Wistar-Kyoto rats, a putative animal model of depression. RESULTS: Chronic AMPA treatment resulted in a dose-dependent antidepressant effect in both the forced swim test and sucrose preference test. Moreover, chronic administration (10-11 days) of combinations of AMPA and ketamine, at doses that were ineffective on their own, resulted in a significant antidepressant effect. The behavioral effects were associated with increases in hippocampal brain-derived neurotrophic factor, synapsin, and mammalian target of rapamycin. CONCLUSION: These findings are the first to provide evidence for an antidepressant effect of AMPA and suggest the usefulness of AMPA-ketamine combination in treatment of depression. Furthermore, these effects appear to be associated with increases in markers of hippocampal neurogenesis and synaptogenesis, suggesting a mechanism of their action.
Authors: Fabio Fumagalli; Francesca Calabrese; Alessia Luoni; Mohammed Shahid; Giorgio Racagni; Marco A Riva Journal: Pharmacol Res Date: 2011-11-03 Impact factor: 7.658
Authors: Jesse S O Lindholm; Henri Autio; Liisa Vesa; Hanna Antila; Lothar Lindemann; Marius C Hoener; Phil Skolnick; Tomi Rantamäki; Eero Castrén Journal: Neuropharmacology Date: 2011-08-16 Impact factor: 5.250
Authors: L Diniz; T B dos Santos; L R G Britto; I C Céspedes; M C Garcia; R C Spadari-Bratfisch; C C Medalha; G M de Castro; F T Montesano; M B Viana Journal: Behav Brain Res Date: 2012-10-22 Impact factor: 3.332
Authors: Marije aan het Rot; Katherine A Collins; James W Murrough; Andrew M Perez; David L Reich; Dennis S Charney; Sanjay J Mathew Journal: Biol Psychiatry Date: 2010-01-15 Impact factor: 13.382
Authors: Sungho Maeng; Carlos A Zarate; Jing Du; Robert J Schloesser; Joseph McCammon; Guang Chen; Husseini K Manji Journal: Biol Psychiatry Date: 2007-07-23 Impact factor: 13.382
Authors: Marzena Mackowiak; Michael J O'Neill; Caroline A Hicks; David Bleakman; Phil Skolnick Journal: Neuropharmacology Date: 2002-07 Impact factor: 5.250
Authors: Eric J Lenze; Nuri B Farber; Evan Kharasch; Julie Schweiger; Michael Yingling; John Olney; John W Newcomer Journal: World J Biol Psychiatry Date: 2016-02-26 Impact factor: 4.132
Authors: Ingeborg H Hansen; Claus Agerskov; Lars Arvastson; Jesper F Bastlund; Helge B D Sørensen; Kjartan F Herrik Journal: Eur J Neurosci Date: 2019-04-01 Impact factor: 3.386
Authors: Zuleide M Ignácio; Gislaine Z Réus; Camila O Arent; Helena M Abelaira; Meagan R Pitcher; João Quevedo Journal: Br J Clin Pharmacol Date: 2016-01-08 Impact factor: 4.335