• Natural Product Sciences
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• v.22 no.4
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• pp.263-269
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• 2016

Rhynchophylline (RP) is a major tetracyclic oxindole alkaloid of Uncariae Ramulus et Uncus which has been used to treat hypertension, seizures, pain and anxiety in the oriental countries. A recent report revealed that RP attenuated ischemia-induced neuronal damage and kainite-induced convulsions in animals. This study was performed to investigate whether RP enhances pentobarbital-induced sleep behaviors and modulates sleep architecture in mice. Locomotor activity was significantly inhibited by RP at 0.25 and 0.5 mg/kg, similar to 2 mg/kg diazepam (a benzodiazepine agonist) in mice. RP shortened sleep latency and increased total sleep time in a dose-dependent manner when administrated with pentobarbital (42 mg/kg, i.p.). RP also increased the number of sleeping mice and total sleep time by concomitant administration with the sub-hypnotic dosage of pentobarbital (28 mg/kg, i.p.). On the other hand, RP (0.25 mg/kg, p.o.) itself significantly inhibited sleep-wake cycles, prolonged total sleep time, and rapid eye movement in rats. In addition, RP also increased chloride influx in the primary cultured hypothalamic neuronal cells. In addition, we found that glutamic acid decarboxylase ($GAD_{65/67}$) was activated by RP. In conclusion, RP augments pentobarbital-induced sleeping behaviors, and can be a candidate for treating insomnia.

• Journal of Ginseng Research
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• v.31 no.4
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• pp.217-221
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• 2007

Ginseng has been widely used for the management of anxiety and emotional instability, but there is little experimental evidence supporting these clinical applications. The anxiolytic-like effect of ginseng saponin and polysaccharide fractions of white (WG) and red ginsengs (RG) was investigated using the elevated plus-maze test. The saponin (SF) and polysaccharide (PF) fractions were orally administered to male ICR mice for 3 days and behavioral test for the anxiolytic activity were performed. SF significantly increased the time-spent open arms and number into the in the open arm entries. However, PF weakly increased the time-spent in the open arms, but did not increase number into the open ann entries. The WG showed more potent anxiolytic-like effect than that of RG. The anxiolytic-like activities were antagonized by flumazenil, but not by esmolol. These findings suggest the saponin fractions of WG and RG promote the anxiolytic-like activity by antagonizing GABN/benzodiazepine receptors in mice.

• The Korean Journal of Physiology
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• v.30 no.1
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• pp.97-104
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• 1996

Different neural substrates have been reported to be implicated in analgesic mechanisms in the acute phasic and the sustained tonic pains. To explore the differential antinociceptive action of diphenylhydantoin (DPH) and carbamazepine (CBZ) on the acute phasic and the tonic pains, changes in tail flick latency, hot plate latency and the formalin-induced nociceptive score were assessed prior to and after intraperitoneal administration of DPH (20 & 40 mg/Kg) and CBZ (20 mg/Kg). In 11 rats, CBZ was administered repeatedly for 6 days at the dose of 20 mg/Kg/day. Also studied were the effects of strychnine and picrotoxin (1 mg/Kg, i.p.) on the CBZ-produced changes in the formalin-induced pain behaviors. The tail flick and hot plate ltencies were not changes after administration of DPH and CBZ. However DPH strongly suppressed the formalin-induced tonic pain. A single and the repeated administration of CBZ inhibited both the early phasic and the late tonic pain responses to formalin in n similar manner. On the other hand, the antinociceptive actions of CBZ were not altered by strychnine or picrotoxin. These experimental findings lead to the conclusion that DPH and CBZ have differential antinociceptive action on the acute and the tonic pains and that their antinociceptive actions are independent of the GABA- and glycine-receptors.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.6
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• pp.303-307
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• 2006

The effects of ethanol on corticostriatal synaptic transmission were examined, using extracellular recording and analysis of population spike amplitudes in rat brain slices, to study how acute ethanol intoxication impairs striatal function. Ethanol caused a decrease in population spike amplitudes in a dose dependent manner ($50{\sim}200mM$). Pretreatment with picrotoxin, a ${\gamma}-amino$ butyric acid $(GABA)_{A}$ receptor antagonist, increased the population spikes but ethanol (100 mM) was still effective in decreasing the population spikes under this condition. In the presence of $_{(DL)}-2-amino-5-phosphonovaleric$ acid (APV), N-methyl-D-aspartate (NMDA) receptor antagonist, the inhibitory action of ethanol on population spikes was not shown. These results suggest that ethanol inhibits the glutamatergic corticostriatal synaptic transmission through blockade of NMDA receptors.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.27-40
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• 1992

The purpose of the present study is an attempt to investigate the effect of intraventricular taurine, which is a naturally occuring amino acid containing sulfur and has inhibitory action in brain, on heart rate and blood pressure in the urethane anesthetized rabbits and also to elucidate the mechanism of its cardiovascular actions. Taurine $(0.15{\sim}1.5\;mg)$ injected into the lateral ventricle of anesthetized normontensive rabbits produced a dose-related fall in arterial blood pressure and heart rate, which were marked and long-lasting along with considerable respiratory depression. However, the intravenous administration of taurine at the same dose with intraventricular injection did not induce any changes in blood pressure as well as heart rate. Depressor responses induced by taurine were inhibited significantly by pretreatment with chlorisondamine, clonidine, strychnine and bicuculline but not by atropine, vagotomy, propranolol and metoclopramide. Moreover, taurine did not affect the pressor responses of norepinephrine. Taurine-induced bradycardic effects were blocked clearly by pretreatment with chlorisondamine, propranolol, clonidine, strychnine and bicuculline, while they were not influenced by atropine, vagotomy and metoclopramide. These experimental results suggest that intraventricular taurine causes long-lasting hypotensive and bradycardic actions, and that these cardiovascular effects may be exerted through taurinergic (glycinergic) and GABAergic receptors which are associated with catecholaminergic neurons in brain.

• Biomolecules & Therapeutics
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• v.27 no.6
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• pp.584-590
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• 2019

Luteolin, a widespread flavonoid, has been known to have neuroprotective activity against various neurologic diseases such as epilepsy, and Alzheimer's disease. However, little information is available regarding the hypnotic effect of luteolin. In this study, we evaluated the hypnotic effect of luteolin and its underlying mechanism. In pentobarbital-induced sleeping mice model, luteolin (1, and 3 mg/kg, p.o.) decreased sleep latency and increased the total sleep time. Through electroencephalogram (EEG) and electromyogram (EMG) recording, we demonstrated that luteolin increased non-rapid eye movement (NREM) sleep time and decreased wake time. To evaluate the underlying mechanism, we examined the effects of various pharmacological antagonists on the hypnotic effect of luteolin. The hypnotic effect of 3 mg/kg of luteolin was not affected by flumazenil, a GABAA receptorbenzodiazepine (GABAAR-BDZ) binding site antagonist, and bicuculine, a GABAAR-GABA binding site antagonist. On the other hand, the hypnotic effect of 3 mg/kg of luteolin was almost completely blocked by caffeine, an antagonist for both adenosine A1 and A2A receptor (A1R and A2AR), 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), an A1R antagonist, and SCH-58261, an A2AR antagonist. From the binding affinity assay, we have found that luteolin significantly binds to not only A1R but also A2AR with $IC_{50}$ of 1.19, $0.84{\mu}g/kg$, respectively. However, luteolin did not bind to either BDZ-receptor or GABAAR. From these results, it has been suggested that luteolin has hypnotic efficacy through A1R and A2AR binding.

• Journal of the Korean Magnetic Resonance Society
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• v.24 no.4
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• pp.104-116
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• 2020

Fipronil, the phenylpyrazole insecticide, is effective and used in various fields. Especially, fipronil was reliable because it was known to be specific on invertebrate animals than vertebrate animals including mammals. However, fipronil had potential risks that affect vertebrate animals as it blocks the gamma-aminobutyric acid (GABA) receptors that also exists in vertebrates as well as invertebrates. Therefore, it was necessary that harmful effects of fipronil on vertebrates are clarified. For this purpose, the zebrafish (Danio rerio) were used on behalf of vertebrate animals in present study. The zebrafish were exposed to 5 ㎍/L, 25 ㎍/L, and 50 ㎍/L of fipronil during 12, 24 and 72 hours. To closely observe toxic process, 12 hours and 24 hours of additional time point were set in the exposure test. Nuclear magnetic resonance (NMR)-based metabolomics is an approach to detect metabolic changes in organism resulted from external stimuli. In this study, NMR-based metabolomics showed the metabolic changes in zebrafish caused by fipronil exposure. Metabolic analysis revealed that fipronil interfered with energy metabolism and decreased the antioxidant ability in zebrafish. Antioxidant ability decline was remarkable at high exposure concentration. In addition, metabolic analysis results over time suggested that reactions for alleviating the excessive nerve excitation occurred in zebrafish after fipronil exposure. Through this study, it was elucidated that the adverse effects of fipronil on vertebrate animals are evident. The risk of fipronil on vertebrates can be no longer ignored. Moreover, this study has a meaning of practically necessary research for organism by examining the effects of fipronil at low concentrations existed in real environment.

• Journal of Veterinary Science
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• v.25 no.5
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• pp.63.1-63.12
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• 2024

Importance: Glutamic acid decarboxylase 67 (GAD67) is a gamma-aminobutyric acid (GABA) synthesis enzyme associated with the function of other neurotransmitter receptors, such as the N-methyl-D-aspartate (NMDA) receptor and cannabinoid receptor 1. However, the role of GAD67 in the development of different abused drug-induced reward behaviors remains unknown. In order to elucidate the mechanisms of substance use disorder, it is crucial to study changes in biomarkers within the brain's reward circuit induced by drug use. Objective: The study was designed to examine the effects of the downregulation of GAD67 expression in the dorsal striatum on reward behavior development. Methods: We evaluated the effects of GAD67 knockdown on depression-like behavior and anxiety using the forced swim test and elevated plus maze test in a mouse model. We further determined the effects of GAD67 knockdown on ketamine- and JWH-018-induced conditioned place preference (CPP). Results: Knockdown of GAD67 in the dorsal striatum of mice increased depression-like behavior, but it decreased anxiety. Moreover, the CPP score on the NMDA receptor antagonist ketamine was increased by GAD67 knockdown, whereas the administration of JWH-018, a cannabinoid receptor agonist, did not affect the CPP score in the GAD67 knockdown mice group compared with the control group. Conclusions and Relevance: These results suggest that striatal GAD67 reduces GABAergic neuronal activity and may cause ketamine-induced NMDA receptor inhibition. Consequently, GAD67 downregulation induces vulnerability to the drug reward behavior of ketamine.

• Nutrition Research and Practice
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• v.12 no.3
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• pp.199-207
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• 2018

BACKGROUND/OBJECTIVES: Fermented Laminaria japonica (FL), a type sea tangle used as a functional food ingredient, has been reported to possess cognitive improving properties that may aid in the treatment of common neurodegenerative disorders, such as dementia. MATERIALS/METHODS: We examined the effects of FL on scopolamine (Sco)- and ethanol (EtOH)-induced hippocampus-dependent memory impairment, using the Passive avoidance (PA) and Morris water maze (MWM) tests. To examine the underlying mechanisms associated with neuroprotective effects, we analyzed acetylcholine (ACh) and acetylcholinesterase (AChE) activity, brain tissue expression of muscarinic acetylcholine receptor (mAChR), cAMP response element binding protein (CREB) and extracellular signal-regulated kinases 1/2 (ERK1/2), and immunohistochemical analysis, in the hippocampus of mice, compared to current drug therapy intervention. Biochemical blood analysis was carried out to determine the effects of FL on alanine transaminase (ALT), aspartate transaminase (AST), and triglyceride (TG) and total cholesterol (TC) levels. 7 groups (n = 10) consisted of a control (CON), 3 Sco-induced dementia and 3 EtOH-induced dementia groups, with both dementia group types containing an untreated group (Sco and EtOH); a positive control, orally administered donepezil (Dpz) (4mg/kg) (Sco + Dpz and EtOH + Dpz); and an FL (50 mg/kg) treatment group (Sco + FL50 and EtOH + FL50), orally administered over the 4-week experimental period. RESULTS: FL50 significantly reduced EtOH-induced increase in AST and ALT levels. FL50 treatment reduced EtOH-impaired step-through latency time in the PA test, and Sco- and EtOH-induced dementia escape latency times in the MWM test. Moreover, anticholinergic effects of Sco and EtOH on the brain were reversed by FL50, through the attenuation of AChE activity and elevation of ACh concentration. FL50 elevated ERK1/2 protein expression and increased p-CREB (ser133) in hippocampus brain tissue, according to Western blot and immunohistochemistry analysis, respectively. CONCLUSION: Overall, these results suggest that FL may be considered an efficacious intervention for Sco- and EtOH-induced dementia, in terms of reversing cognitive impairment and neuroplastic dysfunction.