• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.102-102
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• 1997

The purpose of this study was to determine the behavioral interaction between glutamatergic and serotonergic receptors. In the present study, both the competitive (AP-5 and D-CPP) and the noncompetitive (MK-801, ketamine, dextrorphan and dextromethorphan) N-methyl-D-aspartate (NMDA) receptor antagonists markedly enhanced 5-HT(5-hydroxytryptamine)-induced selective serotonergic behavior, head-twitch response (HTR), in mice. These results suggest that the glutamatergic neurotransmission may modulate serotonergic function at the 5-HT receptor. The precise relationship between glutamatergic and serotonergic system is as yet undefined. However, these are the first data available regarding glutamatergic modulation of serotonergic function at the 5-HT receptor in intact mice, and the present results support the notion that the NMDA receptors may play important roles in the glutamatergic modulation of serotonergic function at the 5-HT receptor.

• Archives of Pharmacal Research
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• v.11 no.4
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• pp.301-307
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• 1988

Relationship between the maintenance of hypertension and central serotonergic nervous system activity in opontaneously hypertensive rats (SHR) was studied. Serotonin turnover-rates were measured in 5 brain areas as an index of serotonergic neuronal activity and compared at the ages of 14 weeks in two types of animals; (1) spontaneously hypertensive rats (SHR) (2) normotensive wistar kyoto rats (WKY). In 14-week old SHR, central serotonin turnover rate was significantly lower in telencephalon, hypothalamus/thalamus and midbrain than normotensive rat, but significantly higher in cerebellum. There were no significant differences between serotonin turnover rate in pons/medulla of SHR and that of normotensive rat. THese data suggest that the abnormally lower turnover rates of serotonin in telencephalon, hypothalamus/thalamus and midbrain may be one of the underlying neuronal factors for manifestation of hypertension in SHR.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.335-335
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• 1994

Possibility whether lead ingestion can cause selective toxicity to central serotonergic nervous system in rats was tested. Three groups of wistar rats; 1)Control, 2) Low dose and 3) High dose groups, were prepared. In prenatally lead-exposed rats, until parturition from dams, rat pups were intoxicated via placenta of mother rats having received drinking water containing either 0%(control ), 0.05%(low dose) or 0.2%(high dose) of lead acetate respectively, In postnatally lead-exposed rats, right after parturition from dams rat pups received drinking water containing either 0％ (control), 0.05%(low dose) or 0.2％(high dose) of lead acetate. At 2, 4, 6 and 8 weeks of age, tryptophan hydroxylase (TPH) activity and Na$\^$+//K$\^$+/-ATPase activity were measured in 4 areas of rat brain; Telencephalon, Diencephalon, Midbrain and Pons/Medulla. TPH activities were assayed by modified method of Beevers et al. (1983) using L-(5-$^3$H)-tryptophan as substrate. TPH activity was determined as a criterion of lead poisoning to central serotonergic nervous system and Na$\^$+//K$\^$+/-ATPase activity as a criterion of non specific lead poisoning to any kinds of tissues. Selective toxicity of lead poisoning to central serotonergic nervous system was evaluated by the changes of TPH activities without concomitant changes of Na$\^$+//K$\^$+/-ATPase activities. In prenatally lead-exposed rats. this selectivity was found in Telencephalon (2 weeks of age), Diencephalon/Midbrain (2 weeks of age), Midbrain (4 and 6 weeks of age), Pons/Medulla (2, 4 and 6 weeks of age) In rats exposed to low dose of lead and Pons/Medulla (2 weeks of age) to high dose of lead. In postnatal Iy lead-exposed rats, this selectivity was found in Telencephalon (8 weeks of age), Diencephalon(8 weeks of age), Pons/Medulla (6 and 8 weeks of age) in rats exposed to low dose of lead and Pons/Medulla (8 weeks of age) to high dose of lead. These results suggest that lead poisoning may exhibit selective toxicity to central serotonergic nervous system.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.3
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• pp.149-153
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• 2005

The aim of the present study was to determine whether serotonergic drugs could reverse lipopolysaccharide (LPS)-induced anorexia in rats. LPS ($500{\mu}g$/kg body weight) and all serotonergic drugs, except for 8-OH-DPAT (subcutaneous), were injected intraperitoneally into Sprague-Dawley rats. Without the LPS injection, 8-OH-DPAT (1A agonist), metergoline (1/2 antagonist), and mianserin (2A/2C antagonist) exerted no effects on food intake at any of the doses tested, but ketanserin (2A antagonist) caused an increase of food intake at 4 mg/kg. RS-102221 (2C antagonist) reduced food intake at 2 and 4 mg/kg. LPS reduced food intake 1 hour after injection, and food intake remained low until the end of measurement period (24 hours) (p<0.05). Pretreatment of rats with 8-OH-DPAT partially recovered of cumulative food intake at all measured times (2, 4, 6, 8, and 24 hours after LPS injection). Pretreatment with metergoline resulted in a partial recovery of cumulative food intake at 2, 4, 6, and 8 hours, but not at 24 hours. Ketanserin caused partial recovery at 2 and 4 hours only. Mianserin and RS-102221 had no effects on LPS-reduced food intake. A variety of serotonergic drugs ameliorated anorexic symptoms, which suggesting that the serotonin system plays a role in LPS-induced anorexia.

• The Korean Journal of Pharmacology
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• v.25 no.1
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• pp.1-11
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• 1989

In this study, it was aimed to investigate the role of serotonergic neurotransmission in nucleus tractus solitarius (NTS) for the central regulation of blood pressure and heart rate and its involvement in baroreceptor reflex activation in rats. A microinjection of 5-hydroxytryptamine (5-HT) into the NTS produced decreases in blood pressure and heart rate. Maximal decreases were $34.4{\pm}1.6$ mmHg and $41.7{\pm}10.2$ beats per min by 300 pmol of 5-HT. Microinjections of ${\alpha}-methylnor-adrenaline$ $({\alpha}-MNE)$ and clonidine manifested similar decreases in blood pressure and heart rate. The hypotensive and bradycardial effects of 5-HT were blocked by previous applications of 5-HT antagonists, ritanserin, methysergide and ketanserin into the NTS, respectively. By pretreatment with reserpine and 6-hydroxydopamine (6-OHDA, i.c.v.), both hypotensive and bradycardial effects of 5-HT were significantly attenuated. Pretreatment with 5, 7-dihydroxytryptamine (5,7-DHT, i.c.v.) enhanced the hypotensive and bradycardial effects of 5-HT. Similarly, following pretreatment with 6-OHDA, the effects of clonidine were increased. Pretreatment either with 5,7-DHT or 6-OHDA significantly attenuated the sensitivity of baroreflex produced either by phenylephrine or by sodium nitroprusside. When either 5,7-DHT or 6-OHDA was injected into the NTS $(5,7-DHT;\;8{\mu}g\;6-OHDA;\;10{\mu}g)$, both of the baroreflex sensitivities were impaired. In the immunohistochemical study, the injection of 6-OHDA into the the NTS led to reduction of axon terminal varicosity, however, the injection did not reduce the numbers of catecholaminergic cell bodies. Likewise, when 5,7-DHT was injected into the NTS, the varicosity of serotonergic axon terminals was markedly reduced. Based on these results, it is suggested that (1) stimulation of serotonergic receptors in the NTS leads to decreases in blood pressure and heart rate as observed with the stimulation of catecholaminergic system, (2) both serotonergic and catecholaminergic receptors may be located postsynaptically, and (3) the serotonergic neurons as well as catecholaminergic neurons may have a close relevance for the activation of baroreflex.

• The Korean Journal of Pharmacology
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• v.26 no.1
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• pp.1-6
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• 1990

We established an in vitro system of central serotonergic neurons by culturing dissociated rat embryonic (El4) brainstem cells to 14 days in vitro and monitored the serotonergic neuronal growth by measuring 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) contents in the cells with hish performance liquid chromatography with electrochemical detection (HPLC-EC). We studied also tile effects of various drugs on the contents of 5-HT and 5-HIAA, confirming in vivo reports. The 5-HT content (13 ng/mg protein) and 5-HT turnover rate (17 pmol/mg protein/h) at 14 days in vitro were in good agreement with those reported in the adult rat brain. The 5-HT content was more easily depleted with p-chlorophenylalanine, a tryptophan hydroxylase inhibitor than with NSD 1015 (3-hydroxybenzylhydrazine), an aromatic L-amino acid decarboxylase (AADC) inhibitor. Incubation of the cultures with tryptophan or 5-hydroxytryptophan increased the rate of serotonin formation implying that neither tryptophan hydroxylase nor AADC is saturated with its amino acid substrate in this in vitro system . The 5-HT content was depleted by reserpine. The 5-HT and 5-HIAA contents were increased and decreased, respectively, by monoamine oxidase inhibitors. All the above results indicate that the biochemical properties of the central serotonergic neurons in this culture system reflect reliably those of central serotonergic neurons in vivo. We suggest that measuring 5-HT and 5-HIAA contents in the primary cultured dissociated brainstem-cells with HPLC-EC is useful in the study of pharmacology as well as toxicolgy of the central serotonergic neurons.

• Journal of Acupuncture Research
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• v.17 no.2
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• pp.119-138
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• 2000

This study was designed to evaluate the effect of the bee venom(BV) aqua-acupuncture on the neuronal activities of serotonergic(5-HT) system in the brainstem. After the BV aqua-acupuncture was applied on Chok-Samni(ST36) and the gluteal part(Blank locus) in rats, the number of Fos immunoreactive neurons was counted by using computerized image analyzing system. Also, the number of colocalization between 5-HT containing neurons Fos immunoreactive neurons were analyzed by using the double immunohistochemical technique. The results of the experiments were summarized as follows : 1. In almost every neucli, the Chok-Samni group and Blank locus group showed more increase in the number of Fos immunoreactive neurons than the control group. Especially, in Arc, DR, LC, RMg, Gi, PAG Rost and PAG LV, the Chok-Samni group showed more significant increase than the control group. Also, in PAG LV Mid and Arc, Chok-Samni group showed more significant increase than the Blank locus group. 2. In DR and PAG LV Mid, Chok-Samni group and the Blank locus group showed more significant increase in the number of colocalization between 5-HT containing neurons and Fos immunoreactive neurons than the control group after the BV aqua- acupuncture. Also, the Chok-Samni group showed more significant increase than the Blank locus group. Consequently, the BV aqua-acupuncture increased more potent the number of Fos immunoreactive neurons and the activity of serotonergic neurons. Furthermore, the BV aqua-acupuncture was more effective on Chok-Samni than Blank locus group. These results indicate that the BV aqua-acupuncture is very effective therapy to control pain. The therapeutic effect of BV aqua-acupunture may associated with the endogenous modulatory system such as serotonin Those data from the study can be applied to establish the effective treatment of the BV for pain control in the clinical field.

• Korean Journal of Veterinary Research
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• v.33 no.1
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• pp.71-80
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• 1993

The central nervous system depressant effect of xylazine and xylazine-ketamine was studied in chicken and mice. Intraperitoneal injection of xylazine(1~30 mg/kg) and xylazine(1~30 mg/kg)-ketamine(100 mg/kg) induced a loss of the righting reflex in chicken and mice, respectively. These effects of xylazine were dose-dependent. The results obtained were as follows; 1. The effect of xylazine-induced depression was antagonized by adrenergic antagonists having ${\alpha}_2$-blocking activity(yohimbine, tolazoline, piperoxan and phentolamine). 2. Yohimbine was most effective in the reduction of the CNS depression by xylazine. 3. Phenoxybenzamine and prazosin did not reduced CNS depression by xylazine in both species. 4. Labetalol (${\alpha}_1$, ${\beta}_1$-adrenergic antagonist) and propranolol(${\beta}$-adrenergic blocking agent) were not effective in reducing xylazine induced depression. 5. Cholinergic blocking agents (atropine and mecamylamine), a dopaminergic antagonist (Haloperidol), a histamine $H_1$-antagonist(chlorpheniramine), a histamine $H_2$-antagonist(cimetidine), a serotonergic-histamine $H_1$ antagonist(cyproheptadine) were not effective in reducing xylazine-induced depression. 6. Xylazine-induced depression is mediated by ${\alpha}_2$-adrenergic receptors and appears not to be involved in cholinergic, dopaminergic, serotonergic or histaminergic pathways.

• Archives of Pharmacal Research
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• v.13 no.1
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• pp.55-63
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• 1990

An attempt was made to investigate the effect of intracerebroventricular 5-hydroxytrypatamine (5-HT) on the cardiovascular system in urethane-anesthetized rabbit and to elucidate the mechanism of its action. 5-HT given into a lateral ventricle caused clearly a dose-dependent decrease inboth arterial blood pressure and in heart rate. The bradycardia and hypotension induced by 5-HT were significantly attenuated by the prior injection of ketanserin, cyproheptadine or clonidine. Pretreatment of atropine with bilateral vagotomy did not affect both bradycardia and hypotension. Propranolol weakened markedly the breadcardia of 5-HT but did not influence the depressor response of 5-HT. These experimental results suggest that intraventricular 5-HT cause the hypotension and bradyardia in rabbits through the stimulation of serotonergic receptors in brain, which is seemed to be associated to inhibition of sympathetic tone.

• Journal of Yeungnam Medical Science
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• v.38 no.4
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• pp.371-373
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• 2021

Serotonin syndrome (SS) is a potentially life-threatening condition that is caused by the administration of drugs that increase serotonergic activity in the central nervous system. We report a case of serotonin syndrome in a patient with chronic pain who was taking analgesic drugs. A 36-year-old female with chronic pain in the lower back and right buttock area had been taking tramadol hydrochloride 187.5 mg, acetaminophen 325 mg, pregabalin 150 mg, duloxetine 60 mg, and triazolam 0.25 mg daily for several months. After amitriptyline 10 mg was added to achieve better pain control, the patient developed SS, which was mistaken for psychogenic nonepileptic seizure. However, her symptoms completely disappeared after discontinuation of the drugs that were thought to trigger SS and subsequent hydration with normal saline. Various drugs that can increase serotonergic activity are being widely prescribed for patients with chronic pain. Clinicians should be aware of the potential for the occurrence of SS when prescribing pain medications to patients with chronic pain.