Chronic fluoxetine treatment induces structural plasticity and selective changes in glutamate receptor subunits in the rat cerebral cortex

Ampuero, Estíbaliz; Rubio, Francisco J.; Falcon, Romina; Sandoval, Mauricio; Dı́az-Véliz, Gabriela; González, Rodolfo; Earle, Nicholas; Dagnino‐Subiabre, Alexies; Aboitiz, Francisco; Orrego, Fernando; Wyneken, Úrsula

doi:10.1016/j.neuroscience.2010.04.035

Cited by 122 publications

(113 citation statements)

References 79 publications

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“…Indeed, ketamine possesses a rich pharmacology, including activity at sigma receptors (123,124). Moreover, actions within dopaminergic (125)(126)(127) or serotonergic (128)(129)(130)(131)(132) systems have also been postulated as alternate mechanisms for ketamine's antidepressant effects. Conversely, ketamine's unique antidepressant properties may be attributable to distinctions in its pharmacodynamic activity within the NMDA receptor (34,122).…”

Section: Discussionmentioning

confidence: 99%

Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression

Newport¹,

Carpenter²,

McDonald³

et al. 2015

AJP

520

377

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The antidepressant efficacy of ketamine, and perhaps D-cycloserine and rapastinel, holds promise for future glutamate-modulating strategies; however, the ineffectiveness of other NMDA antagonists suggests that any forthcoming advances will depend on improving our understanding of ketamine's mechanism of action. The fleeting nature of ketamine's therapeutic benefit, coupled with its potential for abuse and neurotoxicity, suggest that its use in the clinical setting warrants caution.

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Section: Discussionmentioning

confidence: 99%

Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression

Newport¹,

Carpenter²,

McDonald³

et al. 2015

AJP

520

377

View full text Add to dashboard Cite

show abstract

“…The decreased spinophilin expression might be indicative of a specific transient decrease in dendritic spine density, which is likely to result from remodelling of hippocampal dendritic spines density. Thus, previous studies using chronic fluoxetine showed remodelling of dendritic spines towards a mushroom type rather than changing dendritic spines density per se (Bessa et al 2009;Ampuero et al 2010). In the amygdala, synaptophysin, PSD-95 and spinophilin were all increased by agomelatine treatment suggesting neuronal remodelling and changes in synaptic connections.…”

Section: Vehicle Agomelatinementioning

confidence: 93%

Agomelatine (S20098) modulates the expression of cytoskeletal microtubular proteins, synaptic markers and BDNF in the rat hippocampus, amygdala and PFC

Ladurelle

Gabriel

Viggiano³

et al. 2011

Psychopharmacology

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“…Instead, the dendritic and synaptic remodeling were the primary changes associated with behavioral deficits caused by CUS and the improvements resulting from antidepressant treatments. Although fluoxetine alone had no effect, another study found that chronic fluoxetine administration increases spine density in retrosplenial granular cortex [1]. This study also reported that chronic fluoxetine treatment that produced antidepressant behavioral responses in rodent models of depression and anxiety, resulted in up-regulation of N-methyl-D-aspartate (NMDA) receptor subunit NR2A, and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits GluR1 and 2 in forebrain [1].…”

Section: Antidepressant Effects On Spines and Synaptic Markersmentioning

confidence: 99%

Spine synapse remodeling in the pathophysiology and treatment of depression

Duman

2015

Neuroscience Letters

230

184

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Clinical brain imaging and postmortem studies provide evidence of structural and functional abnormalities of key limbic and cortical structures in depressed patients, suggesting that spine synapse connectivity is altered in depression. Characterization of the cellular determinants underlying these changes in patients are limited, but studies in rodent models demonstrate alterations of dendrite complexity and spine density and function that could contribute to the morphological and functional alterations observed in humans. Rodent studies demonstrate region specific effects in chronic stress models of depression, including reductions in dendrite complexity and spine density in the hippocampus and prefrontal cortex (PFC) but increases in the basolateral amygdala and nucleus accumbens. Alterations of spine synapse connectivity in these regions are thought to contribute to the behavioral symptoms of depression, including disruption of cognition, mood, emotion, motivation, and reward. Studies of the mechanisms underlying these effects demonstrate a role for altered brain derived neurotrophic factor (BDNF) signaling that regulates synaptic protein synthesis. In contrast, there is evidence that chronic antidepressant treatment can block or reverse the spine synapse alterations caused by stress. Notably, the new fast acting antidepressant ketamine, which produces rapid therapeutic actions in treatment resistant MDD patients, rapidly increases spine synapse number in the PFC of rodents and reverses the effects of chronic stress. The rapid synaptic and behavioral actions of ketamine occur via increased BDNF regulation of synaptic protein synthesis. Together these studies provide evidence for a neurotophic and synaptogenic hypothesis of depression and treatment response and indicate that spine synapse connectivity in key cortical and limbic brain regions is critical for control of mood and emotion.

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Chronic fluoxetine treatment induces structural plasticity and selective changes in glutamate receptor subunits in the rat cerebral cortex

Cited by 122 publications

References 79 publications

Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression

Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression

Agomelatine (S20098) modulates the expression of cytoskeletal microtubular proteins, synaptic markers and BDNF in the rat hippocampus, amygdala and PFC

Spine synapse remodeling in the pathophysiology and treatment of depression

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