1. Hypothetical mechanism of ketamine’s antidepressant effects
Hypothetical mechanism of ketamine’s antidepressant effects. It is speculated that ketamine increases extracellular glutamate levels in prefrontal cortex, possibly via antagonism of NMDA receptors on GABAergic interneurons resulting in disinhibition of glutamaterigc transmission. This leads to activity-dependent release of BDNF and stimulation of TrkB signaling cascades, including AKT, that activate the mTOR translational system in dendrites of neurons. Induction of translation would then increase levels of the AMPA receptor subunit GluA1 and other synaptic proteins, providing the machinery required for increased synaptogenesis and spine formation. (Reproduced with permission from Duman RS, Li N. A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists. Philos Trans R Soc Lond B Biol Sci. 2012;367(1601):2475–2484.)
Source: Mood and Emotion, Molecular Neuropharmacology: A Foundation for Clinical Neuroscience, 3e
Citation: Nestler EJ, Hyman SE, Holtzman DM, Malenka RC. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience, 3e; 2015 Available at: Accessed: October 24, 2017
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