Palmatine plays a role in sedation and hypnosis by increasing 5-hydroxytryptamine

Abstract

Objective of this study was to investigate the sedative and hypnotic effects of palmatine and to observe whether its mechanism is related to 5-hydroxytryptamine (5-HT) and GABA. The sedative and hypnotic effects of palmatine on mice were observed with mouse autonomic activity test, direct sleep test, pentobarbital sodium in suprathreshold and subthreshold dose sleep test. The content of GABA and 5-HT in brain homogenate was determined by ELISA method. Mouse brain specimens were observed by immunohistochemistry for 5-HT expression in the nucleus of mouse brain. Palmatine could reduce spontaneous activities of mice, prolong the sleep time of mice induced by pentobarbital sodium in suprathreshold dose and shorten the sleep latency. And it could increase the number of mice falling asleep induced by pentobarbital sodium in subthreshold dose and the incidence of falling asleep, but with no direct sleep effect. In addition, it enhanced the 5-HT content in brain, but had no effect on GABA content, and had no toxicity to PC12 cells. Palmatine plays a significant role in sedation and hypnosis, which may be associated with the increase of intra-cerebral 5-HT.

The Influence of Palmatine Isolated from Berberis sibirica Radix on Pentylenetetrazole-Induced Seizures in Zebrafish

“…Deprenyl (MAO inhibitor) exposure significantly increased serotonin content in the brain of developing larval zebrafish and decreased their locomotion and altered vertical positioning [68]. PALM-induced reduction of locomotor activity was previously noted in mice [59]. In the present study, we did not observe changes of locomotor activity in PALM-only-treated zebrafish larvae, which could be due to relatively low ability of PALM to elicit MAO inhibition and/or participation of other mediators, i.e., tryptophan hydroxylase, that regulate serotonin level in the brain [68].…”

“…extracts, BERB, both in rodents and zebrafish [22][23][24]. However, although CNS-related effects of PALM have been investigated [56][57][58][59][60], until now, no evidence has existed for its activity in animal seizure and epilepsy models. Here, we demonstrated for the first time the anticonvulsant activity of PALM, which decreased the number of epileptiform-like discharges recorded in the brain of PTZ-treated zebrafish larvae.…”

“…The anticonvulsant activity of numerous GABAmimetic compounds, including some clinically used ASDs, has been previously proved in the zebrafish larvae PTZ seizure assay [10,62,63]. However, this mechanism of anticonvulsant effect of the studied alkaloids might be also questioned because it was demonstrated that PALM did not change the GABA content in the mouse brain [59], and BERB was able to inhibit the GABA A receptor at approximately 60% [64].…”

“…The engagement of the GABA-benzodiazepine pathway in this regard was also considered [57]. On the other hand, sedative and hypnotic effects of PALM were linked to changes in concentration of neurotransmitters, i.e., dopamine and serotonin, in brain structures [58,59]. It was found that PALM exerted antidepressant activity in the tail suspension, sucrose preference, and forced swim tests both in stressed and unstressed mice.…”