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Antidepressive and anxiolytic effects of ostruthin, a TREK-1 channel activator.
- Source :
- PLoS ONE; 8/14/2018, Vol. 13 Issue 8, p1-19, 19p
- Publication Year :
- 2018
-
Abstract
- We screened a library of botanical compounds purified from plants of Vietnam for modulators of the activity of a two-pore domain K<superscript>+</superscript> channel, TREK-1, and we identified a hydroxycoumarin-related compound, ostruthin, as an activator of this channel. Ostruthin increased whole-cell TREK-1 channel currents in 293T cells at a low concentration (EC<subscript>50</subscript> = 5.3 μM), and also activity of the TREK-2 channel (EC<subscript>50</subscript> = 3.7 mM). In contrast, ostruthin inhibited other K<superscript>+</superscript> channels, e.g. human ether-à-go-go-related gene (HERG1), inward-rectifier (Kir2.1), voltage-gated (Kv1.4), and two-pore domain (TASK-1) at higher concentrations, without affecting voltage-gated potassium channel (KCNQ1 and 3). We tested the effect of this compound on mouse anxiety- and depression-like behaviors and found anxiolytic activity in the open-field, elevated plus maze, and light/dark box tests. Of note, ostruthin also showed antidepressive effects in the forced swim and tail suspension tests, although previous studies reported that inhibition of TREK-1 channels resulted in an antidepressive effect. The anxiolytic and antidepressive effect was diminished by co-administration of a TREK-1 blocker, amlodipine, indicating the involvement of TREK-1 channels. Administration of ostruthin suppressed the stress-induced increase in anti-c-Fos immunoreactivity in the lateral septum, without affecting immunoreactivity in other mood disorder-related nuclei, e.g. the amygdala, paraventricular nuclei, and dorsal raphe nucleus. Ostruthin may exert its anxiolytic and antidepressive effects through a different mechanism from current drugs. [ABSTRACT FROM AUTHOR]
- Subjects :
- HYDROXY acids
COUMARINS
T cells
ANTIDEPRESSANTS
TRANQUILIZING drugs
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 13
- Issue :
- 8
- Database :
- Complementary Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 131237226
- Full Text :
- https://doi.org/10.1371/journal.pone.0201092