Ethanol Induces Sedation and Hypnosis via Inhibiting Histamine Release in Mice.

Ethanol is one of the most highly abused psychoactive compounds worldwide and induces sedation and hypnosis. The histaminergic system is involved in the regulation of sleep/wake function and is a crucial player in promoting wakefulness. To explore the role and mechanism of the histaminergic system in ethanol-induced sedation and hypnosis, we recorded locomotor activity (LMA) and electroencephalography (EEG)/electromyography (EMG) in mice using an infrared ray passive sensor recording system and an EEG/EMG recording system, respectively, after administration of ethanol. In vivo microdialysis coupled with high performance liquid chromatography and fluorometry technology were used to detect histamine release in the mouse frontal cortex (FrCx). The results revealed that ethanol significantly suppressed LMA of histamine receptor 1 (H1R)-knockout (KO) and wild-type (WT) mice in the range of 1.5-2.5 g/kg, but suppression was remarkably stronger in WT mice than in H1R-KO mice. At 2.0 and 2.5 g/kg, ethanol remarkably increased non-rapid eye movement sleep and decreased wakefulness, respectively. Neurochemistry experimental data indicated that ethanol inhibited histamine release in the FrCx in a dose-dependent manner. These findings suggest that ethanol induces sedation and hypnosis via inhibiting histamine release in mice.

[Protective effect of paeonol on neurotoxicity induced by Abeta1-42 and underlying mechanisms].

OBJECTIVE: To investigate the protective effect of paeonol on amyloid beta1-42 (Abeta1-42)-induced neurotoxicity and its mechanism. METHOD: Hippocampal neurons of well-grown newborn SD rats and differentiated SH-SY5Y cell lines were cultured with various concentrations of paeonol (1, 5, 10 micromol x L(-1), respectively) for 6 hours and then incubated with Abeta1-42 oligomer (30 micromol x L(-1)) for 24 hours and 48 hours, respectively. The neuron apoptosis was observed by Heochst33258. Annexin V/PI double stain flow cytometry assay was adopted for determining SH-SY5Y cell apoptosis rate. And the expression of BDNF and Bcl-2 mRNA was detected by RT-PCR. RESULT: Compared with the model group, various concentrations of paeonol (1, 5, 10 micromol x L(-1)) significantly reduced the hippocampal neurons karyopycnosis, decreased the rate of SH-SY5Y cell apoptosis to 22.4%, 18.1% and 16.4%, respectively, and improved the expressions of BDNF and Bcl-2 mRNA. CONCLUSION: Paeonol relieves Abeta1-42 oligomer-induced neuron injury by increasing BDNF and Bcl-2 expressions.

Safranal enhances non-rapid eye movement sleep in pentobarbital-treated mice.

AIMS: Safranal (2,6,6-trimethyl-1,3-cyclohexadiene-1-carboxaldehyde, C(10) H(14) O) is an active ingredient in the saffron, which is used in traditional medicine. It has been reported to have sedative and anti-epileptic effects, but its hypnotic effects remain uncertain. The aim of this study was to evaluate effects of safranal on sleep-wake cycle. METHODS: We established hypnotic-model mice treated with a low dose of pentobarbital 20 mg/kg, and administered different doses of safranal, vehicle, or diazepam. The change of sleep-wake cycle was assessed by sleep recording and c-Fos expression in the brain was analyzed by immunohistochemistry. RESULTS: Safranal increased the duration of non-rapid eye movement (NREM) sleep, shortened NREM sleep latency, and enhanced the delta power activity of NREM sleep. Immunohistochemical evaluation revealed that safranal increased c-Fos expression in the ventrolateral preoptic nucleus (VLPO), one of the putative sleep centers, and decreased it in the arousal histaminergic tuberomammillary nuclei (TMN). CONCLUSION: These findings indicate that safranal enhances NREM sleep in pentobarbital-treated mice. The hypnotic effects of safranal may be related to the activation of the sleep-promoting neurons in the VLPO and the simultaneous inhibition of the wakefulness-promoting neurons in the TMN, suggesting that safranal may be a hypnotic substance.

[Anti-inflammation effect of danggui shaoyao san on Alzheimer's diseases].

OBJECTIVE: To study the mechanisms of Danggui Shaoyao San (DSS) on Alzheimer's diseases (AD) focusing on anti-inflammation. METHOD: AD rats were established by intrahippocampal bilateral injection of Abeta1-42 protein. The AD rats were randomly divided into three groups: AD model group, DSS high-dose group, DSS low-dose group. Vehicle group rats were intrahippocampal bilateral injection of solvent with the same dose. The learning ability and memory of rats was investigated in step-down passive avoidance test and Morris water maze test, expression of IL-1beta, IL-6, TNF-alpha mRNA were observed by reverse transcriptase PCR (RT-PCR), levels of NO was measured by colorimetric method and neuron apoptosis in the hippocampus was investigated by tag method of TdT-mediated end-labeling of fragmented DNA (TUNEL). RESULT: DSS significantly reduced the escape latency and increased the time that rats spent in the target quadrant in Morris water maze test, shortened the responsive latency and decreased the error numbers in step-down passive avoidance test, reduced the expression of the IL-1beta, IL-6, TNF-alpha mRNA, and the level of the NO depressed the neuron apoptosis in the hippocampus. CONCLUSION: DSS improving cognition of the rats might be related to attenuate inflammatory reaction and reduce cell apoptosis in the hippocampus.

[Tissue distribution in mice of danshensu from sodium danshensu and Salvia miltiorrhiza injection].

OBJECTIVE: To determine the concentration in mice of danshensu from sodium danshensu and Salvia miltiorrhiza injection and undertake comparative study of them as well as to assess the effect of other components of S. miltiorrhiza injection on the tissue distribution of danshensu. METHOD: Mice received intraperitoneal administration of sodium danshensu or S. miltiorrhiza injection (equal to danshensu 60 mg x kg(-1)) respectively, and was executed 30 minutes after administration. The concentration of danshensu in different tissues was separately determined by high performance liquid chromatographic method. RESULT: The characteristic profiles of sodium danshensu in different tissues were C(kidney) > C(spleen) > C(lung) > C(heart) > C(liver). The characteristic profiles of danshensu from S. miltiorrhiza injection in different tissues were C(kidney) > C(lung) > C(spleen) > C(heart) approximately C(liver). The concentration of danshensu in S. miltiorrhiza injection in liver and kindey was higher than sodium danshensu itself. CONCLUSION: It was suggested that the other components in S. miltiorrhiza injection influent the distribution profile in tissues of danshensu.

[Comparative pharmacokinetic study of sodium Danshensu and Salvia miltiorrhiza injection in rat].

OBJECTIVE: To develop a HPLC method for determination of the concentration of Danshensu in rat plasma and undertake comparative pharmacokinetic study of sodium danshensu and Salvia miltiorrhiza injection in rat as well as to assess the effect of other components of Salvia miltiorrhiza injection on the pharmacokinetics of Danshensu. METHOD: Rats received an iv. infusion of sodium Danshensu or S. miltiorrhiza injection (equal to Danshensu 30 mg x kg(-1)). Blood samples were collected from carotid artery. Plasma concentration of Danshensu extracted with perchloric acid was measured. The pharmacokinetic parameters were calculated with DAS2.0 software. RESULT: A good linear relationship of Danshensu was obtained from the range of 0.5 to 80.0 mg x L(-1), and the lowest limit of determination was 0.2 mg x L(-1). The plasma concentration time curves of Danshensu were best fitted with two-compartment models for Danshensu itself and for Salvia miltiorrhiza injection as well. The pharmacokinetic parameters such as t1/2alpha, AUC, CL had significant differences. CONCLUSION: The concomitant components in Salvia miltiorrhiza injection influence the pharmacokinetic properties of Danshensu and speed up its disposition and elimination.

An adenosine A receptor agonist induces sleep by increasing GABA release in the tuberomammillary nucleus to inhibit histaminergic systems in rats.

The adenosine A(2A) receptor (A(2A)R) has been demonstrated to play a crucial role in the regulation of the sleep process. However, the molecular mechanism of the A(2A)R-mediated sleep remains to be elucidated. Here we used electroencephalogram and electromyogram recordings coupled with in vivo microdialysis to investigate the effects of an A(2A)R agonist, CGS21680, on sleep and on the release of histamine and GABA in the brain. In freely moving rats, CGS21680 applied to the subarachnoid space underlying the rostral basal forebrain significantly promoted sleep and inhibited histamine release in the frontal cortex. The histamine release was negatively correlated with the amount of non-rapid eye movement sleep (r = - 0.652). In urethane-anesthetized rats, CGS21680 inhibited histamine release in both the frontal cortex and medial pre-optic area in a dose-dependent manner, and increased GABA release specifically in the histaminergic tuberomammillary nucleus but not in the frontal cortex. Moreover, the CGS21680-induced inhibition of histamine release was antagonized by perfusion of the tuberomammillary nucleus with a GABA(A) antagonist, picrotoxin. These results suggest that the A(2A)R agonist induced sleep by inhibiting the histaminergic system through increasing GABA release in the tuberomammillary nucleus.