The role of hippocampal GABA A receptors on anxiolytic effects of Echium amoenum extract in a mice model of restraint st
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ORIGINAL ARTICLE
The role of hippocampal GABAA receptors on anxiolytic effects of Echium amoenum extract in a mice model of restraint stress Fereshteh Farajdokht1,2 · Armin Vosoughi1 · Mojtaba Ziaee3,4 · Mostafa Araj‑Khodaei5 · Javad Mahmoudi1 · Saeed Sadigh‑Eteghad1,5,6 Received: 13 April 2020 / Accepted: 26 July 2020 © Springer Nature B.V. 2020
Abstract Echium amoenum (EA), a popular medicinal plant in Persian medicine, has anxiolytic, antioxidant, sedative, and anti-inflammatory effects. This study examined whether GABA-ergic signaling is involved in the anxiolytic effects of EA in mice. Sixty BALB/c mice (25–30 g) were divided into six groups (n = 10) as follows: the (I) control group received 10 ml/kg normal saline (NS). In the stress groups, the animals underwent 14 consecutive days of restraint stress (RS), and received following treatments simultaneously; (II) RS + NS; (III) RS + Diaz (Diazepam); (IV) RS + EA; (V) RS + Flu (Flumazenil) + EA; (VI) RS + Flu + Diaz. Behavioral tests including the open field test (OFT) and elevated plus maze (EPM) were performed to evaluate anxiety-like behaviors and the effects of the regimens. The plasma level of corticosterone and the hippocampal protein expressions of IL-1β, TNF-α, CREB, and BDNF, as well as p-GABAA/GABAA ratio, were also assessed. The findings revealed that chronic administration of EA alone produced anxiolytic effects in both behavioral tests, while diazepam alone or in combination with Flu failed to decrease the anxiety-like behaviors. Furthermore, the p-GABAA/GABAA and p-CREB/CREB ratios, and protein levels of BDNF were significantly increased in the EA-received group. On the other hand, plasma corticosterone levels and the hippocampal IL-1β and TNF-α levels were significantly decreased by EA. However, pre-treatment with GABAA receptors ( GABAA Rs) antagonist, Flu, reversed the anxiolytic and molecular effects of EA in the RS-subjected animals. Our findings confirmed that alternation of G ABAAR is involved in the effects of EA against RSinduced anxiety-like behaviors, HPA axis activation, and neuroinflammation. Keywords Anxiety · Echium amoenum · GABAA receptors · CREB · BDNF · Inflammation
Introduction
* Saeed Sadigh‑Eteghad [email protected] 1
Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz 5166614756, Iran
2
Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
3
Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4
Phytopharmacology Research Center, Maragheh University of Medical Sciences, Maragheh, Iran
5
Department of Persian Medicine, Faculty of Persian Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
6
East‑Azerbaijan Comprehensive Stroke Program, Tabriz University of Medical Sciences, Tabriz, Iran
Anxiety is a common psychological problem during the last decade in many modern societies mostly due to a stressful lifestyle. Anxiety leads to weight changes, anhedonia, fatigue,
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