Strategies for producing faster acting antidepressants

Adell, Albert; Castro, Elena; Celada, Pau; Bortolozzi, A.; Pazos, Ángel; Artigas, Francesc

doi:10.1016/s1359-6446(05)03398-2

Cited by 122 publications

(69 citation statements)

References 76 publications

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“…It has been hypothesized that the late onset of action of SSRIs is due to negative feedback circuitry, mediated via 5-HT 1A autoreceptors (Hjorth et al, 2000); therefore, compounds that are inhibitors of SERT and agonists of 5-HT 1A receptors have been pursued as improved antidepressants (Adell et al, 2005;Dawson and Bromidge, 2008). Two compounds, vilazodone and Lu AA21004 (Fig.…”

Section: B Novel Principles For Treatment Of Mood Disordersmentioning

confidence: 99%

SLC6 Neurotransmitter Transporters: Structure, Function, and Regulation

et al. 2011

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Section: B Novel Principles For Treatment Of Mood Disordersmentioning

confidence: 99%

SLC6 Neurotransmitter Transporters: Structure, Function, and Regulation

et al. 2011

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“…Recent evidence suggests that the well documented delay in antidepressant efficacy (Adell et al, 2005) may be attributable to neural adaptive mechanisms to reverse the damage of stress in the hippocampus including changes in synaptic plasticity, neurogenesis, and synaptogenesis (Castren, 2005;Dranovsky and Hen, 2006;WarnerSchmidt and Duman, 2006). These modifications of neuronal function most likely require the transcription of new molecules.…”

Section: Introductionmentioning

confidence: 99%

The Neuropeptide VGF Produces Antidepressant-Like Behavioral Effects and Enhances Proliferation in the Hippocampus

Krol²,

et al. 2007

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Brain-derived neurotrophic factor (BDNF) is upregulated in the hippocampus by antidepressant treatments, and BDNF produces antidepressant-like effects in behavioral models of depression. In our previous work, we identified genes induced by BDNF and defined their specific roles in hippocampal neuronal development and plasticity. To identify genes downstream of BDNF that may play roles in psychiatric disorders, we examined a subset of BDNF-induced genes also regulated by 5-HT (serotonin), which includes the neuropeptide VGF (nonacronymic). To explore the function of VGF in depression, we first investigated the expression of the neuropeptide in animal models of depression. VGF was downregulated in the hippocampus after both the learned helplessness and forced swim test (FST) paradigms. Conversely, VGF infusion in the hippocampus of mice subjected to FST reduced the time spent immobile for up to 6 d, thus demonstrating a novel role for VGF as an antidepressant-like agent. Recent evidence indicates that chronic treatment of rodents with antidepressants increases neurogenesis in the adult dentate gyrus and that neurogenesis is required for the behavioral effects of antidepressants. Our studies using

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Section: Introductionmentioning

confidence: 99%

“…The immediate effect of SSRIs on the inhibition of 5-HT uptake in vitro is in contrast to their delayed therapeutic effect [15]. Several lines of evidence suggest that the changes in sensitivity of somatodendritic 5-HT 1A and/or terminal 5-HT 1B autoreceptors [15,16] could have beneficial effect on the clinical response to acute antidepressant treatment. The controversy around the association between acute SSRI administration and suicidal behaviour in adults [17] and adolescents [18] may also be due to the unclear acute effect of antidepressants on the serotonergic system.…”

Section: Introductionmentioning

confidence: 99%

Acute treatment with fluvoxamine elevates rat brain serotonin synthesis in some terminal regions: An autoradiographic study

Mück‐Šeler

Pivac

Dikšić

2012

Nuclear Medicine and Biology

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Introduction-A considerable body of evidence indicates the involvement of the neurotransmitter serotonin (5-HT) in the pathogenesis and treatment of depression.Methods-The acute effect of fluvoxamine, on 5-HT synthesis rates was investigated in rat brain regions, using α-14 C-methyl-L-tryptophan as a tracer. Fluvoxamine (25 mg/kg) and saline (control) were injected intraperitoneally, one hour before the injection of the tracer (30 μCi).Results-There was no significant effect of fluvoxamine on plasma free tryptophan. After Benjamini-Hochberg False Discovery Rate correction, a significant decrease in the 5-HT synthesis rate in the fluvoxamine treated rats, was found in the raphe magnus (−32%), but not in the median (−14%) and dorsal (−3%) raphe nuclei. In the regions with serotonergic axon terminals, significant increases in synthesis rates were observed in the dorsal (+41%) and ventral (+43%) hippocampus, visual (+38%), auditory (+65%) and parietal (+37%) cortex, and the substantia nigra pars compacta (+56%). There were no significant changes in the 5-HT synthesis rates in the median (+11%) and lateral (+24%) part of the caudate-putamen, nucleus accumbens (+5%), VTA (+16%) or frontal cortex (+ 6%).Conclusions-The data show that the acute administration of fluvoxamine affects 5-HT synthesis rates in a regionally specific pattern, with a general elevation of the synthesis in the terminal regions and a reduction in some cell body structures. The reasons for the regional specific effect of fluvoxamine on 5-HT synthesis are unclear, but may be mediated by the presynaptic serotonergic autoreceptors. Keywords

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Strategies for producing faster acting antidepressants

Cited by 122 publications

References 76 publications

SLC6 Neurotransmitter Transporters: Structure, Function, and Regulation

SLC6 Neurotransmitter Transporters: Structure, Function, and Regulation

The Neuropeptide VGF Produces Antidepressant-Like Behavioral Effects and Enhances Proliferation in the Hippocampus

Acute treatment with fluvoxamine elevates rat brain serotonin synthesis in some terminal regions: An autoradiographic study

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