Subchronic vortioxetine treatment -but not escitalopram- enhances pyramidal neuron activity in the rat prefrontal cortex

NEUROPHARMACOLOGY

卷:113

Article

Riga, Maurizio S.^1,2,3  Teruel-Marti, Vicent⁴  Sanchez, Connie⁵  Celada, Pau^1,2,3  Artigas, Francesc^1,2,3 

[1] CSIC IDIBAPS, Dept Neurochem & Neuropharmacol, Inst Invest Biomed Barcelona, Barcelona, Spain

[2] CIBERSAM Ctr Invest Biomed Red Salud Mental, Madrid, Spain

[3] Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain

[4] Univ Valencia, Dept Human Anat & Embriol, Fac Med & Odontol, E-46003 Valencia, Spain

[5] Lundbeck AS Valby, Valby, Denmark

关键词: 5-hydroxytryptamine (serotonin);    5-HT3 receptors;    Antidepressants;    Medial prefrontal cortex;    Pyramidal neurons;   

DOI  :  10.1016/j.neuropharm.2016.09.024

来源: Elsevier

【 摘 要 】

Vortioxetine Vortioxetine (VOR) is a multimodal antidepressant drug. VOR is a 5-HT3-R, 5-HT7-R and 5-HT1D-R antagonist, 5-HT1B-R partial agonist, 5-HT1A-R agonist, and serotonin transporter (SERT) inhibitor. VOR shows pro-cognitive activity in animal models and beneficial effects on cognitive dysfunction in major depressive patients. Here we compared the effects of 14-day treatments with VOR and escitalopram (ESC, selective serotonin reuptake inhibitor) on neuronal activity in the medial prefrontal cortex (mPFC). Ten groups of rats (5 standard, 5 depleted of 5-HT with p-chlorophenylalanine -pCPA-, used as model of cognitive impairment) were fed with control food or with two doses of VOR-containing food. Four groups were implanted with minipumps delivering vehicle or ESC 10 mg/kg.day s.c. The two VOR doses enable occupation by VOR of SERT+5-HT3-R and all targets, respectively, and correspond to SERT occupancies in patients treated with 5 and 20 VOR mg/day, respectively. Putative pyramidal neurons (n = 985) were recorded extracellularly in the mPFC of anesthetized rats. Sub-chronic VOR administration (but not ESC) significantly increased neuronal discharge in standard and 5-HT-depleted conditions, with a greater effect of the low VOR dose in standard rats. VOR increased neuronal discharge in infralimbic (IL) and prelimbic (PrL) cortices. Hence, oral VOR doses evoking SERT occupancies similar to those in treated patients increase mPFC neuronal discharge. The effect in 5-HT depleted rats cannot be explained by an antagonist action of VOR at 5-HT3-R and suggests a non canonical interaction of VOR with 5-HT3-R. These effects may underlie the superior pro-cognitive efficacy of VOR compared with SSRIs in animal models. (C) 2016 Elsevier Ltd. All rights reserved.

【 授权许可】

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