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01-06-2014 | Original Paper

Attenuation of Reserpine-Induced Pain/Depression Dyad by Gentiopicroside Through Downregulation of GluN2B Receptors in the Amygdala of Mice

Authors: Shui-bing Liu, Rong Zhao, Xu-sheng Li, Hong-ju Guo, Zhen Tian, Nan Zhang, Guo-dong Gao, Ming-gao Zhao

Published in: NeuroMolecular Medicine | Issue 2/2014

Abstract

Epidemiological studies demonstrate that pain frequently occurs comorbid with depression. Gentiopicroside (Gent) is a secoiridoid compound isolated from Gentiana lutea that exhibits analgesic properties and inhibits the expression of GluN2B-containing N-methyl-d-aspartate (NMDA) receptors in the anterior cingulate cortex of mice. However, the effects of Gent on the reserpine-induced pain/depression dyad and its underlying mechanisms are unclear. Reserpine administration (1 mg/kg subcutaneous daily for 3 days) caused a significant decrease in the nociceptive threshold as evidenced by the reduced paw withdrawal latency in response to a radiant heat source and mechanical allodynia. Behavioral detection indicated a significant increase in immobility time during a forced swim test, as well as decreased time in the central area and total travel distance in an open field test. Furthermore, reserpinized animals exhibited increased oxidative stress. Systemic Gent administration dose-dependently ameliorated the behavioral deficits associated with reserpine-induced pain/depression dyad. At the same time, the decrease in biogenic amine levels (norepinephrine, dopamine, and serotonin) was integrated with the increase in caspase-3 levels and GluN2B-containing NMDA receptors in the amygdala of the reserpine-injected mice. Gent significantly reversed the changes in the levels of biogenic amines, caspase-3, and GluN2B-containing NMDA receptors in amygdala. However, Gent did not affect the expression of GluN2A-containing NMDA receptors. The inhibitory effects of Gent on oxidative stress were occluded by simultaneous treatment of GluN2B receptors antagonist Ro25-6981. Our study provides strong evidence that Gent inhibits reserpine-induced pain/depression dyad by downregulating GluN2B receptors in the amygdala.

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Title: Attenuation of Reserpine-Induced Pain/Depression Dyad by Gentiopicroside Through Downregulation of GluN2B Receptors in the Amygdala of Mice
Authors: Shui-bing Liu
Rong Zhao
Xu-sheng Li
Hong-ju Guo
Zhen Tian
Nan Zhang
Guo-dong Gao
Ming-gao Zhao
Publication date: 01-06-2014
Publisher: Springer US
Published in: NeuroMolecular Medicine / Issue 2/2014
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-013-8280-8

At a glance: The STEP trials

Springer Medicine

Attenuation of Reserpine-Induced Pain/Depression Dyad by Gentiopicroside Through Downregulation of GluN2B Receptors in the Amygdala of Mice

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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