Determination of five neurotransmitters in the rat brain for the study of the hypnotic effects of Ziziphi Spinosae Semen aqueous extract on insomnia rat model by UPLC-MS/MS

Sep 14, 2019Chinese journal of natural medicines

Measuring brain chemicals in rats to study how Ziziphi Spinosae Semen extract may help with insomnia

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Abstract

Levels of serotonin, GABA, and dopamine were significantly lower in an insomnia rat model, while glutamic acid and noradrenaline were significantly higher.

Insomnia induced by para-chlorophenylalanine led to altered neurotransmitter levels in the rat brain.
Significantly lower concentrations of serotonin, GABA, and dopamine were observed in the insomnia model compared to controls.
Conversely, levels of glutamic acid and noradrenaline were significantly higher in the insomnia model.
Treatment with Ziziphi Spinosae Semen aqueous extract for seven days may improve insomnia symptoms by normalizing neurotransmitter levels.
The developed method for analyzing neurotransmitters showed strong linearity and was efficient, completing in under 10 minutes.

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Ziziphi Spinosae Semen (ZSS) has been used for treatment of insomnia in China for centuries. To reveal the influence of insomnia on the levels of the neurotransmitters including serotonin (5-HT), glutamic acid (Glu), γ-aminobutyric acid (GABA), noradrenaline (NE) and dopamine (DA), and to study the role of ZSS aqueous extract in the treatment of insomnia, an UPLC-ESI- MS/MS method was developed and validated for simultaneous determination of five neurotransmitters in the rat brain. The brain samples were pretreated by one-step direct protein precipitation with acetonitrile. The analytes were detected in positive mode with multiple reaction monitoring (MRM) and the procedure was completed in less than 10 min. The method showed a good linearity (R> 0.9967) with the other validation parameters were within acceptance range. The results indicated that the concentration of 5-HT, GABA and DA is significantly lower (P < 0.01) in para-chlorophenylalanine (PCPA)-induced insomnia rat model group, while Glu and NE significantly higher than those in control group (P < 0.01). Treatment with ZSS aqueous extract (4 or 8 g·kg·dfor seven days) could ameliorate the symptoms of insomnia by significantly changing the levels of the neurotransmitter parameters mentioned above. The data obtained in this study demonstrate that ZSS aqueous extract could ameliorate the symptoms of insomnia by modulating the levels of monoamines and amino acid neurotransmitters in the brain. 2 -1 -1

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Determination of five neurotransmitters in the rat brain for the study of the hypnotic effects of Ziziphi Spinosae Semen aqueous extract on insomnia rat model by UPLC-MS/MS

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