Back to Search
Start Over
Quercetin relieves D-amphetamine-induced manic-like behaviour through activating TREK-1 potassium channels in mice.
- Source :
-
British journal of pharmacology [Br J Pharmacol] 2021 Sep; Vol. 178 (18), pp. 3682-3695. Date of Electronic Publication: 2021 Jun 08. - Publication Year :
- 2021
-
Abstract
- Background and Purpose: Quercetin is a well-known plant flavonoid with neuroprotective properties. Earlier work suggested it may relieve psychiatric disorders, cognition deficits and memory dysfunction through anti-oxidant and/or radical scavenging mechanisms. In addition, quercetin modulated the physiological function of some ion channels. However, the detailed ionic mechanisms of the bioeffects of quercetin remain unknown.<br />Experimental Approach: Effects of quercetin on neuronal activities in the prefrontal cortex (PFC) and its ionic mechanisms were analysed by calcium imaging using mice bearing a green fluorescent protein, calmodulin, and M13 fusion protein and patch clamp in acute brain slices from C57BL/6 J mice and in HEK 293 cells. The possible ionic mechanism of action of quercetin on D-amphetamine-induced manic-like effects in mice was explored with c-fos staining and the open field behaviour test.<br />Key Results: Quercetin reduced calcium influx triggered by PFC pyramidal neuronal activity. This effect involved increasing the rheobase of neuronal firing through decreasing membrane resistance following quercetin treatment. Spadin, a blocker of TREK-1 potassium channels, also blocked the effect of quercetin on the membrane resistance and neuronal firing. Further, spadin blocked the neuroprotective effects of quercetin. The effects of quercetin on TREK-1 channels could be mimicked by GF109203X, a protein kinase C inhibitor. In vivo, injection of quercetin relieved the manic hyperlocomotion in mice, induced by D-amphetamine. This action was partly alleviated by spadin.<br />Conclusion and Implications: TREK-1 channels are a novel target for quercetin, by inhibiting PKC. This action could contribute to both the neuroprotective and anti-manic-like effects.<br /> (© 2021 The British Pharmacological Society.)
Details
- Language :
- English
- ISSN :
- 1476-5381
- Volume :
- 178
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- British journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 33908633
- Full Text :
- https://doi.org/10.1111/bph.15510