Reduced vasopressin receptors activation mediates the anti-depressant effects of fluoxetine and venlafaxine in bulbectomy model of depression

Poretti, María Belén; Sawant, Rahul S.; Rask‐Andersen, Mathias; Cúneo, Marta Fiol de; Schiöth, Helgi B.; Pérez, Mariela Fernanda; Carlini, Valeria Paola

doi:10.1007/s00213-015-4187-4

Cited by 19 publications

(9 citation statements)

References 55 publications

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“…OB was performed according to several previously established surgical protocols 14 , 19 – 21 . Briefly, mice were anesthetized with intraperitoneal injection of ketamine (75 mcg/kg; Troy Laboratories Pty Ltd, USA) and medetomidine (1 mg/kg; Troy Laboratories Pty Ltd, USA).…”

Section: Methodsmentioning

confidence: 99%

Medium- and high-intensity rTMS reduces psychomotor agitation with distinct neurobiologic mechanisms

Heath¹,

Lindberg

Makowiecki

et al. 2018

Transl Psychiatry

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Definitive data are lacking on the mechanism of action and biomarkers of repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression. Low-intensity rTMS (LI-rTMS) has demonstrated utility in preclinical models of rTMS treatments but the effects of LI-rTMS in murine models of depression are unknown. We examined the behavioral and neurobiologic changes in olfactory bulbectomy (OB) mice with medium-intensity rTMS (MI-rTMS) treatment and fluoxetine hydrochloride. We then compared 10-Hz rTMS sessions for 3 min at intensities (measured at the cortical surface) of 4 mT (LI-rTMS), 50 mT (medium-intensity rTMS [MI-rTMS]), or 1 T (high-intensity rTMS [HI-rTMS]) 5 days per week over 4 weeks in an OB model of agitated depression. Behavioral effects were assessed with forced swim test; neurobiologic effects were assessed with brain levels of 5-hydroxytryptamine, brain-derived neurotrophic factor (BDNF), and neurogenesis. Peripheral metabolomic changes induced by OB and rTMS were monitored through enzyme-linked immunosorbent assay and ultrapressure liquid chromatography-driven targeted metabolomics evaluated with ingenuity pathway analysis (IPA). MI-rTMS and HI-rTMS attenuated psychomotor agitation but only MI-rTMS increased BDNF and neurogenesis levels. HI-rTMS normalized the plasma concentration of α-amino-n-butyric acid and 3-methylhistidine. IPA revealed significant changes in glutamine processing and glutamate signaling in the OB model and following MI-rTMS and HI-rTMS treatment. The present findings suggest that MI-rTMS and HI-rTMS induce differential neurobiologic changes in a mouse model of agitated depression. Further, α-amino-n-butyric acid and 3-methylhistidine may have utility as biomarkers to objectively monitor the response to rTMS treatment of depression.

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Section: Methodsmentioning

confidence: 99%

Medium- and high-intensity rTMS reduces psychomotor agitation with distinct neurobiologic mechanisms

Heath¹,

Lindberg

Makowiecki

et al. 2018

Transl Psychiatry

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“…This AVP overdrive can lead to a "switch" in the regulation of the HPA system from CRH to AVP control, resulting in an altered homeostasis within the HPA system with different neurobiological, behavioral, and emotional effects (82) as seen in MDD (91,92). Indeed, MDD is characterized by increased HPA responsiveness to AVP and decreased responsiveness to CRH (82), while antidepressant action is shown to be related to reduction of vasopressinergic overexpression in these patients (40,93). In addition, higher AVP plasma levels in MDD have been associated with distinct depression features, such as melancholic symptoms and psychomotor retardation during the day (86,90,94).…”

Section: Discussionmentioning

confidence: 99%

Vasopressin Surrogate Marker Copeptin as a Potential Novel Endocrine Biomarker for Antidepressant Treatment Response in Major Depression: A Pilot Study

et al. 2020

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Background: Major depressive disorder (MDD) constitutes the leading cause of disability worldwide. Although efficacious antidepressant pharmacotherapies exist for MDD, only about 40-60% of the patients respond to initial treatment. However, there is still a lack of robustly established and applicable biomarkers for antidepressant response in everyday clinical practice.Objective: This study targets the assessment of the vasopressin (AVP) surrogate marker Copeptin (CoP), as a potential peripheral hypothalamic-level biomarker of antidepressant treatment response in MDD.Methods: We measured baseline and dynamic levels of plasma CoP along with plasma ACTH and cortisol (CORT) in drug-naive outpatients with MDD before and after overnight manipulation of the hypothalamic-pituitary-adrenal (HPA) axis [i.e., stimulation (metyrapone) and suppression (dexamethasone)] on three consecutive days and their association with treatment response to 4 weeks of escitalopram treatment.Results: Our findings suggest significantly higher baseline and post-metyrapone plasma CoP levels in future non-responders, a statistically significant invert association between baseline CoP levels and probability of treatment response and a potential baseline plasma CoP cut-off level of above 2.9 pmol/L for future non-response screening. Baseline and dynamic plasma ACTH and CORT levels showed no association with treatment response.Conclusions: This pilot study provide first evidence in humans that CoP may represent a novel, clinically easily applicable, endocrine biomarker of antidepressant response, based on a single-measurement, cut-off level. These findings, underline the role of the vasopressinergic system in the pathophysiology of MDD and may represent a

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“…On the other hand, V 1B receptor antagonists might not have a rapid onset of action. In an olfactory bulbectomy model, SSR149415 exerted antidepressant-like effects after repeated administrations (7, 14, or 28 days), but not after acute administration ( Iijima and Chaki, 2007 ; Breuer et al, 2009 ; Poretti et al, 2016 ). In addition, in a chronic mild stress model, SSR149415 exerted antidepressant-like effects after 7 or 14 days of treatment, similar to conventional antidepressants ( Griebel et al, 2002 ; Alonso et al, 2004 ; Surget et al, 2008 ; Bessa et al, 2009 ).…”

Section: Antidepressant-like Effects and Underlying Mechanisms Of V 1b Receptor Antagonists In Rodentsmentioning

confidence: 93%

Vasopressin V1B Receptor Antagonists as Potential Antidepressants

Chaki

2021

International Journal of Neuropsychopharmacology

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Accumulating evidence shows that certain populations of depressed patients have impaired hypothalamus-pituitary-adrenal (HPA) axis function. Arginine-vasopressin (AVP) is one of primary factors in HPA axis regulation under stress situations, and AVP and its receptor subtype (V1B receptor) play a pivotal role in HPA axis abnormalities observed in depression. Based on this hypothesis, several non-peptide V1B receptor antagonists have been synthesized, and the efficacies of some V1B receptor antagonists have been investigated in both animals and humans. V1B receptor antagonists exert antidepressant-like effects in several animal models at doses that attenuate the hyperactivity of the HPA axis, and some of their detailed mechanisms have been delineated. These results obtained in animal models were, at least partly, reproduced in clinical trials. At least two V1B receptor antagonists (TS-121 and ABT-436) showed tendencies to reduce the depression scores of patients with major depressive disorder at doses that attenuate HPA axis hyperactivity or block the pituitary V1B receptor. Importantly, TS-121 showed a clearer efficacy for patients with higher basal cortisol levels than for those with lower basal cortisol levels, which was consistent with the hypothesis that V1B receptor antagonists may be more effective for patients with HPA axis hyperactivity. Therefore, V1B receptor antagonists are promising approaches for the treatment of depression involving HPA axis impairment such as depression.

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Reduced vasopressin receptors activation mediates the anti-depressant effects of fluoxetine and venlafaxine in bulbectomy model of depression

Cited by 19 publications

References 55 publications

Medium- and high-intensity rTMS reduces psychomotor agitation with distinct neurobiologic mechanisms

Medium- and high-intensity rTMS reduces psychomotor agitation with distinct neurobiologic mechanisms

Vasopressin Surrogate Marker Copeptin as a Potential Novel Endocrine Biomarker for Antidepressant Treatment Response in Major Depression: A Pilot Study

Vasopressin V1B Receptor Antagonists as Potential Antidepressants

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