کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5549137 1402857 2017 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Subchronic vortioxetine treatment -but not escitalopram- enhances pyramidal neuron activity in the rat prefrontal cortex
ترجمه فارسی عنوان
درمان با فرترویسیتین زیر سیکلین - اما نه اسکلیتوپرام - فعال شدن فعالیت نورون های هرمی در قشر پره فرونتول موش صحرایی
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
چکیده انگلیسی


- Unlike escitalopram, subchronic vortioxetine enhances PFC neuronal activity in rats.
- This effect occurs at clinically-relevant oral doses of vortioxetine.
- Vortioxetine increases neuronal discharge in prelimbic and infralimbic cortices.
- Effects in 5-HT-depleted rats suggest a non-canonical interaction with 5-HT3-R.
- These effects may underlie pro-cognitive and antidepressant actions of 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 113, Part A, February 2017, Pages 148-155
نویسندگان
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