Time until relapse after augmentation with single‐dose ketamine in treatment‐resistant depression

Pérez‐Esparza, Rodrigo; Corona, Teresa; Ruiz-Garcia, Ramiro; Oñate‐Cadena, Nelcy; Fuente‐Sandoval, Camilo de la; Ramı́rez-Bermúdez, Jesús

doi:10.1111/pcn.12675

Cited by 5 publications

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References 2 publications

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“…Interestingly, the quest for new drugs for the treatment of major depressive disorder and other psychiatric conditions have shown that ketamine, an NMDAR antagonist, can improve patients' outcome [14][15][16][17]. A single dose of the compound has been shown to elicit favorable effects that last up to a week with minimal adverse side effects [18][19][20]. Investigations into its mechanisms have shown that ketamine not only inhibits NMDAR activities but also regulates the phosphorylation of α-CaMKII (CaMK2A) at the thr286 site in hippocampal dentate gyrus (DG) neurons of depressivelike as well as normal rodents [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Ketamine Induces Lasting Antidepressant Effects by Modulating the NMDAR/CaMKII-Mediated Synaptic Plasticity of the Hippocampal Dentate Gyrus in Depressive Stroke Model

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et al. 2021

Neural Plasticity

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Background. Ketamine has been shown to possess lasting antidepressant properties. However, studies of the mechanisms involved in its effects on poststroke depression are nonexistent. Methods. To investigate these mechanisms, Sprague-Dawley rats were treated with a single local dose of ketamine after middle cerebral artery occlusion and chronic unpredicted mild stress. The effects on the hippocampal dentate gyrus were analyzed through assessment of the N-methyl-D-aspartate receptor/calcium/calmodulin-dependent protein kinase II (NMDAR/CaMKII) pathway, synaptic plasticity, and behavioral tests. Results. Ketamine administration rapidly exerted significant and lasting improvements of depressive symptoms. The biochemical analysis showed rapid, selective upregulation and downregulation of the NMDAR2-β and NMDAR2-α subtypes as well as their downstream signaling proteins β-CaMKII and α-phosphorylation in the dentate gyrus, respectively. Furthermore, the colocalization analysis indicated a significant and selectively increased conjunction of β-CaMKII and postsynaptic density protein 95 (PSD95) coupled with a notable decrease in NMDAR2-β association with PSD95 after ketamine treatment. These changes translated into significant and extended synaptic plasticity in the dentate gyrus. Conclusions. These findings not only suggest that ketamine represents a viable candidate for the treatment of poststroke depression but also that ketamine’s lasting antidepressant effects might be achieved through modulation of NMDAR/CaMKII-induced synaptic plasticity in key brain regions.

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