• The Korean Journal of Physiology and Pharmacology
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• v.6 no.2
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• pp.63-70
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• 2002

Cholinergic modulation of GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) by the activation of muscarine receptors was investigated in mechanically dissociated rat nucleus basalis of the Meynert neurons using the conventional whole-cell patch recording configuration. Muscarine $(10{\mu}M)$ reversibly and concentration-dependently decreased mIPSC frequency without affecting the current amplitude distribution. Muscarine action on GABAergic mIPSCs was completely blocked by $1{\mu}M$ methoctramine, a selective $M_2$ receptor antagonist, but not by $1{\mu}M$ pirenzepine, a selective $M_1$ receptor antagonist. NEM $(10{\mu}M),$ a G-protein uncoupler, attenuated the inhibitory action of muscarine on GABAergic mIPSC frequency. Muscarine still could decrease GABAergic mIPSC frequency even in the $Ca^{2+}-free$ external solution. However, the inhibitory action of muscarine on GABAergic mIPSCs was completely occluded in the presence of forskolin. The results suggest that muscarine acts presynaptically and reduces the probability of spontaneous GABA release, and that such muscarine-induced inhibitory action seems to be mediated by G-protein-coupled $M_2$ receptors, via the reduction of cAMP production. Accordingly, $M_2$ receptor-mediated disinhibition of nBM neurons might play one of important roles in the regulation of cholinergic outputs from nBM neurons as well as the excitability of nBM neurons themselves.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.287-295
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• 1998

Diazepam is known to have cardiovascular depressive effects through a combined action on benzodiazepinergic receptor and the GABA receptor-chloride ion channel complex. Moreover, it is known that barbiturates also have some cardiovascular regulatory effects mediated by the central GABAergic system. Therefore, this study was undertaken to delineate the regulatory actions and interactions of these systems by measuring the responses of the cardiovascular system and renal nerve activity to muscimol, diazepam and pentobarbital, administered intracerebroventricularly in rabbits. When muscimol $(0.03{\sim}0.3\;{\mu}\;g/kg)$, diazepam $(10{\sim}100\;{\mu}\;g/kg)$ and pentobarbital $(1{\sim}10\;{\mu}\;g/kg)$ were injected into the lateral ventricle of the rabbit brain, there were similar dose-dependent decreases in blood pressure (BP) and renal nerve activity (RNA). The relative potency of the three drugs in decreasing BP and RNA was muscimol ＞ pentobarbital ＞ diazepam. Muscimol and pentobarbital also decreased the heart rate in a dose-dependent manner; however, diazepam produced a trivial, dose-independent decrease in heart rate. Diazepam $(30\;{\mu}g/kg)$ augmented the effect of muscimol $(0.1\;{\mu}g/kg)$ in decreasing blood pressure and renal nerve activity, but pentobarbital $(3\;{\mu}g/kg)$ did not. Bicuculline $(0.5\;{\mu}g/kg)$, a GABAergic receptor blocker, significantly attenuated the effect of muscimol in decreasing BP and RNA, either alone or with diazepam, and that of pentobarbital in decreasing BP and RNA, either alone or with muscimol. We inferred that the central benzodiazepinergic and barbiturate systems help regulate peripheral cardiovascular function by modulating the GABAergic system, which adjusts the output of the vasomotor center and hence controls peripheral sympathetic tone. Benzodiazepines more readily modulate the GABAergic system than barbiturates.

• Journal of Oriental Neuropsychiatry
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• v.8 no.1
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• pp.95-109
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• 1997

In order to prove the experimental effectiveness of ChongsimOndamTang by categotizing COTⅠ, COTIⅡ, COTⅢ and COTⅣ according to the volume of COT extract,the anticonvulsion action, the antipyretic action, the analgesic action,the sedative action, and the activity of GABA transaminase, the actuvity concentration of GABA,the activity of GAD in GABAergic system comparing data with control group and observation data show the results as follows.1. The anticonvulsion effect on the convulsion induced by strychine it was significantly effective in COTⅣ and the time to death after the occurrence of the convulsion it was significantly effective in COTⅢ and COTⅣ, and the time to death after the occurrence the convulsion induced by the electrical shock of ECT unit it was significantly effective in all sample groups.2. The hypothemic effect was significantly effective in COT Ⅲ after 1 hour and 2 hour and was significantly effective COTⅣafter 1 hour and 4 hour, and the antipyretic effect on the febrile induced by endotoxin it was significantly effective in COTⅢ every 3 hour and was significantly effective in COTⅣ after 3 hour and 4 hour.3. The analgesic effect was significantly effective in COTⅢ and COTⅣ by decreasing the number of writhing syndrome.4. The sedative effect was decreased significantly all in COTⅢ and COTⅣ after 60 min, 90 min and 120 min.5. The activity of GABA transaminase was decreased significantly in COTⅡ and COTⅢ. 6. The activity concrntration of GABA was increased signifivantly in COTⅡ and COTⅢ. 7. The activity of GAD was increased significantly in COTⅡ and COTⅢ. The results show that ChongsimOndamTang can be an effective cure in mice on the anticonvulsion,the antipyretic , the analgesic,the sedative and the control of the GABAergic system in brain, and it can be used of the epilepsy and convulsive diseases clinically.

• The Korean Journal of Zoology
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• v.33 no.2
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• pp.133-140
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• 1990

In monocular vision, bead and eye optokinetic nystagmus (OKN) display directionnal asymmetry, in lower vertebrates such as chickens, T-N stimulation being more efficient in evoking this visuomotor reflex than N-T stimulation. The N-T component of monocular OKN is significantly weaker in chickens. Coil recordings and observation showed that in adult chickens, prolonged monocular visual deprivation by unilateral eyelid suture provoked significant and progressive increase of the N-T component in chickens. This plasticity phenomenon involved the eye and head OKN in chickens. The administration of THIP, a GABA agonist, abolished reversibly the increase of the N-T component in chickens. This fact suggests that the GABAergic system could be involved in determining this plasticity phenomenon observed in adult lower vertebrates.

• Korean Journal of Oriental Medicine
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• v.2 no.1
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• pp.205-225
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• 1996

This study has been carried out to investigate the effects of Youngyanggaksan (YGS) extract on the anticonvulsive, antipyretic, anlgesic, sedative and GABAergic system of experimental animals. The results of this study were as follows : 1. YGS extract prolonged significantly the beginning time to convulsion and time to death induced by strychnine. 2. YGS extract prolonged significantly the time to death induced by electrical shock of ECT unit (3sec, 200F, 25mA). 3. On the experiment of hypothermic effects of YGS extract on the rectal temperature of rats, YGS extract decreased significantly the rectal temperature of rats. 4. On the experiment of antipyretic effects of YGS extract on the febrile induced by the subcutaneous injection of $150{\mu}g/kg$ endotoxin in rats, YGS extract decreased significantly the rectal temperature of rats. 5. On the experiment of analgesic effects of YGS extract on the writhing syndrome induced by intraperitoneal injection 0.7% acetic acid 1ml/100g in rats, the writhing syndrome was reduced significantly by administration of YGS extract. 6. On the experiment of sedative effects of YGS extract on spontaneous motor activity measured by wheel cage method in mice, the spontaneous motor activity was reduced significantly by administration of YGS extract. 7. On the experiment of effects of YGS extract on the activity of GABA-transaminase(GABA-T) in rat brains after 21 days of oral administration of YGS extract, the activity of GABA-T was reduced significantly by administration of YGS extract. 8. On the experiment of effects of YGS extract on the activity concentration of GABA in rat brains after 21 days of oral administration of YGS extract the activity concentration of GABA was reduced significantly by administration of YGS extract. 9. On the experiment of effects of YGS extract on the activity of GAD in rat brains after 21 days of oral adminstration of YGS extract, the activity of GAD was reduced significantly by administration of YGS extract. According to the those results, Youngyanggaksan extract reveals the effects on the anticonvulsive, antipyretic, anlgesic, sedative and GABAergic system.

• The Korean Journal of Pain
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• v.32 no.3
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• pp.160-167
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• 2019

Background: Pain is a complex mechanism which involves different systems, including the opioidergic and GABAergic systems. Due to the side effects of chemical analgesic agents, attention toward natural agents have been increased. Artemisinin is an herbal compound with widespread modern and traditional therapeutic indications, which its interaction with the GABAergic system and antinoniceptive effects on neuropathic pain have shown. Therefore, this study was designed to evaluate the antinociceptive effects of artemisinin during inflammatory pain and interaction with the GABAergic and opioidergic systems by using a writhing response test. Methods: On the whole, 198 adult male albino mice were used in 4 experiments, including 9 groups (n = 6) each with three replicates, by intraperitoneal (i.p.) administration of artemisinin (2.5, 5, and 10 mg/kg), naloxone (2 mg/kg), bicuculline (2 mg/kg), saclofen (2 mg/kg), indomethacin (5 mg/kg), and ethanol (10 mL/kg). Writhing test responses were induced by i.p. injection of 10 mL/kg of 0.6% acetic acid, and the percentage of writhing inhibition was recorded. Results: Results showed significant dose dependent anti-nociceptive effects from artemisinin which, at a 10 mg/kg dose, was statistically similar to indomethacin. Neither saclofen nor naloxone had antinociceptive effects and did not antagonize antinociceptive effects of artemisinin, whereas bicuculline significantly inhibited the antinocicptive effect of artemisinin. Conclusions: It seems that antinocicptive effects of artemisinin are mediated by $GABA_A$ receptors.

• Journal of Pharmacopuncture
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• v.23 no.1
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• pp.1-7
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• 2020

Nicotine, primary component of tobaco produces craving and withdrawal effect both in humans and animals. Nicotine shows a close resemblance to other addictive drugs in molecular, neuroanatomical and pharmacological, particularly the drugs which enhances the cognitive functions. Nicotine mainly shows its action through specific nicotinic acetylcholine receptors located in brain. It stimulates presynaptic acetylcholine receptors thereby enhancing Ach release and metabolism. Dopaminergic system is also stimulated by it, thus increasing the concentration of dopamine in nuclear accumbens. This property of nicotine according to various researchers is responsible for reinforcing behavioral change and dependence of nicotine. Various researchers have also depicted that some non dopaminergic systems are also involved for rewarding effect of nicotinic withdrawal. Neurological systems such as GABAergic, serotonergic, noradrenergic, and brain stem cholinergic may also be involved to mediate the actions of nicotine. Further, the neurobiological pathway to nicotine dependence might perhaps be appropriate to the attachment of nicotine to nicotinic acetylcholine receptors, peruse by stimulation of dopaminergic system and activation of general pharmacological changes that might be responsible for nicotine addiction. It is also suggested that MAO A and B both are restrained by nicotine. This enzyme helps in degradation dopamine, which is mainly responsible for nicotinic actions and dependence. Various questions remain uninsurable to nicotine mechanism and require more research. Also, various genetic methods united with modern instrumental analysis might result for more authentic information for nicotine addiction.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.4
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• pp.598-601
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• 2010

This experiment was performed to investigate whether the combined-preparation of water extracts of germinated brown rice (WGR), water extracts of cultured mountain ginseng (WCG) and 70% ethanol extracts of Longanae Arillus (ELA) has hypnotic effects and/or enhances pentobarbital-induced sleep behaviors through the GABAergic system. The combined-preparation of WGR and WCG reduced sleep latency and prolonged sleep time induced by pentobarbital. ELA also reduced sleep latency and prolonged sleep time induced by pentobarbital. However, WGR or WCG itself did not induce sleep. The combined-preparation of WGR, WCG and ELA strongly reduced sleep latency and prolonged sleep time via chloride influx into primary cultured cerebellar granule cells. In conclusion, the combined-preparation of WGR, WCG and ELA augments pentobarbital-induced sleep behaviors through the modification of GABAergic system.

• Journal of Life Science
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• v.16 no.5
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• pp.750-758
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• 2006

Calcium-binding protein calretinin is thought to play important roles in calcium buffering. Recently, we reported on the distribution, morphology of calretinin-immunoreactive (IR) neurons and the effects of eye enucleation on the immunoreactivity of calretinin in the superficial layers of the hamster superior colliculus (SC). In the present study, we describe the distributions and types of labeled cells and effects of enucleation in the deeper layers by immunocytochemistry. We also compare this labeling to that of GABA, the major inhibitory neurotransmitter in the central nervous system. In contrast to the superficial layers, the deeper layers contained many calretinin-IR neurons which formed two tiers. The first tier, which was very distinctive, was found within the intermediate gray layer. The second tier was found in the deep gray layer. Labeled neurons varied dramatically in morphology and included vertical fusiform, stellate, round/oval, and horizontal neurons. In contrast to the superficial layers, enucleation appeared to have no effect on the distribution of calretinin immunoreactivity in the deeper layers. Two-color immunofluorescence revealed that none of calretinin-IR neurons were labeled with an antibody to GABA. The present results demonstrate that calretinin identifies unique neuronal sublaminar organizations in the hamster SC. The present results also demonstrate that none of the calretinin-IR neurons in the hamster SC is GABAergic interneurons. As many calretinin-IR cells are GABAergic interneurons in most other brain areas, this phenomenon in hamster SC is exceptional.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.5
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• pp.555-563
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• 1998

The renal function is under regulatory influence of central nervous system (CNS), in which various neurotransmitter and neuromodulator systems take part. However, a possible role of central GABA-benzodiazepine system on the central regulation of renal function has not been explored. This study was undertaken to delineate the renal effects of diazepam. Diazepam, a benzodiazepine agonist, administered into a lateral ventricle (icv) of the rabbit brain in doses ranging from 10 to 100 ${\mu}g/kg,$ elicited dose-related diuresis and natriuresis along with improved renal hemodynamics. However, when given intravenously, 100 ${\mu}g/kg$ diazepam did not produce any significant changes in all parameters of renal function and systemic blood pressure. Diazepam, 100 ${\mu}g/kg$ icv, transiently decreased the renal nerve activity (RNA), which recovered after 3 min. The plasma level of atrial natriuretic peptide (ANP) increased 7-fold, the peak coinciding with the natriuresis and diuresis. Muscimol, a GABAergic agonist, 1.0 ${\mu}g/kg$ given icv, elicited marked antidiuresis and antinatriuresis, accompanied by decreases in systemic blood pressure and renal hemodynamics. When icv 0.3 ${\mu}g/kg$ muscimol was given 3 min prior to 30 ${\mu}g/kg$ of diazepam icv, urinary flow and Na excretion rates did not change significantly, while systemic hypotension was produced. These results indicate that icv diazepam may bring about natriuresis and diuresis by influencing the central regulation of renal function, and that the renal effects are related to the increased plasma ANP levels, not to the decreased renal nerve activity, and suggest that the effects may not be mediated by the activation of central GABAergic system.