Quercetin relieves D-amphetamine-induced manic-like behaviour through activating TREK-1 potassium channels in mice.

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.

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.

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.

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.

• Authors: Keke Ren, Haiying Liu, Baolin Guo, Rui Li, Honghui Mao, Qian Xue, Han Yao, Shengxi Wu, Zhantao Bai, Wenting Wang
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 178 Issue 18 Pg. 3682-3695 (09 2021) ISSN: 1476-5381 [Electronic] England
• PMID: 33908633 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The British Pharmacological Society.

Chemical References

• Potassium Channels, Tandem Pore Domain
• potassium channel protein TREK-1
• Quercetin
• Dextroamphetamine

Topics

• Animals
• Dextroamphetamine
• HEK293 Cells
• Humans
• Mice
• Mice, Inbred C57BL
• Potassium Channels, Tandem Pore Domain
• Quercetin (pharmacology)