New Insight Into the Mechanisms of Fast-Acting Antidepressants: What We Learn From Scopolamine

Anacker, Christoph

doi:10.1016/j.biopsych.2017.11.001

Cited by 7 publications

(5 citation statements)

References 12 publications

(19 reference statements)

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“…Ketamine is a non-competitive N-Methyl-D-aspartate receptor (NMDAR) antagonist investigated for its psychotomimetic properties ( 1 , 2 ) and has, among other NMDAR antagonists, been used to model positive, negative and cognitive symptoms of schizophrenia (SZ) ( 3 , 4 ). More recently, ketamine has gained attention for its robust, long-lasting, rapid-acting antidepressant (RAAD) effects ( 5 , 6 ). The mechanism of therapeutic effect remains un-elucidated and understanding RAAD pathways is complicated by ketamine's affinities to receptors in opioid, norepinephric, dopaminergic and serotonergic systems ( 1 , 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

Activity-State Dependent Reversal of Ketamine-Induced Resting State EEG Effects by Clozapine and Naltrexone in the Freely Moving Rat

et al. 2022

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Section: Introductionmentioning

confidence: 99%

Activity-State Dependent Reversal of Ketamine-Induced Resting State EEG Effects by Clozapine and Naltrexone in the Freely Moving Rat

et al. 2022

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“…Brain-derived neurotrophic factor (BDNF) is integral to depression’s underlying biology and treatment response. , Both ketamine and scopolamine elicit rapid antidepressant effects depending on BDNF . Prior reports show that scopolamine rapidly increases hippocampal BDNF mRNA expression within 8 h, preceding its antidepressant actions .…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Activity Evaluation of Fluorine-Containing Scopolamine Analogues as Potential Antidepressants

Wang,

Zhu,

Wang

et al. 2024

J. Med. Chem.

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This study aimed to develop novel rapid-acting antidepressants with sustained efficacy and favorable safety profiles. We designed and synthesized a series of fluorine-containing scopolamine analogues and evaluated their antidepressant potential. In vitro cytotoxicity assays showed that most of these compounds exhibited minimal toxicity against neuronal and non-neuronal mammalian cell lines (IC 50 > 100 μM). The antidepressant activities of the compounds were evaluated using the tail suspension test, and S-3a was identified as a lead compound with potent and sustained antidepressant effects. Behaviorally, S-3a alleviated depressive symptoms in mice and displayed a higher cognitive safety margin than scopolamine. Toxicological assessments confirmed S-3a's safety, while pharmacokinetics showed a rapid clearance (half-life: 16.6 min). Mechanistically, S-3a antagonized M 1 receptors and elevated BDNF levels, suggesting its potential as an antidepressant for further exploration.

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“…An understanding of the neurobiological basis for individual differences in susceptibility to chronic stress is thus of importance for an understanding of the pathophysiology of mood disorders We sought to provide a comprehensive analysis of differences in neural connectivity that distinguish animals resilient or susceptible to the effects of chronic stress. We examined restingstate brain connectivity in SUS compared with RES mice focusing on the hippocampal vDG, a region critical for the expression of behavioral effects of CSDS (31,32,34,36,37,52). The findings from the current a priori seed-seed and seed-voxel FC analyses distinguished SUS and RES phenotypes following CSDS.…”

Section: General Summarymentioning

confidence: 99%

Resting-state fMRI reveals altered functional connectivity associated with resilience and susceptibility to chronic social defeat stress in mouse brain

Lupinsky,

Nasseef,

Parent

et al. 2024

Preprint

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Chronic stress is a causal antecedent condition for major depressive disorder and associates with altered patterns of neural connectivity. There are nevertheless important individual differences in susceptibility to chronic stress. How stress-induced alterations in functional connectivity amongst depression-related brain regions associates with resilience and susceptibility to chronic stress is largely unknown. We used resting-state functional magnetic resonance imaging (rs-fMRI) to examine functional connectivity between established depression-related regions in susceptible (SUS) and resilient (RES) adult mice following chronic social defeat stress (CSDS). Seed-seed FC analysis revealed that the ventral dentate gyrus (vDG) exhibited the greatest number of group differences in functional connectivity with targeted brain regions. SUS mice showed greater functional connectivity between the vDG and subcortical regions compared to both control (CON) or RES groups. Whole brain vDG seed-voxel analysis supported seed-seed findings in SUS mice and indicated significantly decreased connectivity between the vDG and anterior cingulate area compared to CON mice. Interestingly, RES mice exhibited enhanced connectivity between the vDG and anterior cingulate area compared to SUS mice. Moreover, RES mice showed greater connectivity between the infralimbic prefrontal cortex and the nucleus accumbens shell. These findings indicate unique differences in functional connectivity patterns in SUS and RES mice that could represent a neurobiological basis for vulnerability for stress-induced depression.

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New Insight Into the Mechanisms of Fast-Acting Antidepressants: What We Learn From Scopolamine

Cited by 7 publications

References 12 publications

Activity-State Dependent Reversal of Ketamine-Induced Resting State EEG Effects by Clozapine and Naltrexone in the Freely Moving Rat

Activity-State Dependent Reversal of Ketamine-Induced Resting State EEG Effects by Clozapine and Naltrexone in the Freely Moving Rat

Design, Synthesis, and Activity Evaluation of Fluorine-Containing Scopolamine Analogues as Potential Antidepressants

Resting-state fMRI reveals altered functional connectivity associated with resilience and susceptibility to chronic social defeat stress in mouse brain

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