• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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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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• 제22권2호
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• pp.113-118
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• 1999

Previous work in our laboratory has shown that the N-methyl-D-aspartate (NMDA) receptor antagonists, AP-5, CPP, MK-801, ketamine, dextrorphan and dextromethorphan cause a pronounced enhancement of 5-hydroxytryptamine (5-HT)-induced head-twitch response (HTR) in intact mice, suggesting the involvement of NMDA receptors in the glutamatergic modulation of serotonergic function at the postsynaptic $5-HT_{2}$ receptors. The purpose of this study was to extend our previous work on the behavioral interaction between glutamatergic and serotonergic receptors. In the present study, both competitive (AP-5 and CPP) and noncompeti-tive (MI-801, ketamine, dextrorphan and dextromethorphan) NMDA receptor antagonists markedly enhanced 5-HT-induced selective serotonergic behavior, HTR, in p-chlorophenylalanine (PCPA)-treated mice which were devoid of any involvement of indirect serotonergic function, to establish the involvement of the NMDA receptor in 5-HT-induced HTR at the postsyaptic $5-HT_{2}$receptors. In addition, the enhancement of 5-HT-induced HTR was inhibited by a dopamine agonist, apomorphine, NMDA receptor antagonist, NMDA and a serotonin $5-HT_{2}$receptor antagonist, cyproheptadine, in PCPA-treated mice. Therefore, the present results support our previous conclusion that the NMDA receptors play an important role in the glutamatergic modulation of serotonergic function at the poststynaptic $5-HT_{2}$ receptors.

• 대한한의학회지
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• 제26권3호
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• pp.239-248
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• 2005

Objectives : Electroacupuncture (EA)-induced analgesia has been known to be mediated through the activation of opioid, noradrenergic and serotonergic receptors. However, little study on serotonergic mechanism has been performed in an animal model of chronic pain. The present study was designed to elucidate the type of serotonergic receptors responsible for EA analgesia in the chronic pain model. Methods : In rats with complete Freund's: adjuvant-induced inflammation and spinal nerve injury, spinal wide dynamic range (WDR) cell responses to graded electrical stimulation of afferent C fiber were recorded before and after spinal application of selective 5-hydroxytryptamine (5-HT) receptor antagonists. EA stimulation (2Hz, 0.5msec, 3mA) was applied to the contralateral Zusanli point for 30 min. Results : In both models of chronic pain, WDR cell responses were greatly inhibited after EA stimulation. EA-induced inhibition of WDR celt responses was significantly attenuated by spinal application of non-selective 5-HT receptor antagonist, dihydroergocristine Of 5-HT receptor antagonists tested, 5-HT1A (WAY 100635) and 5-HT2 (LY53857) receptor antagonists strongly reduced an ability of EA stimulation to inhibit WDR cell responses. However, 5-HT1B (GR55562) and 5-HT3 (LY278584) receptor antagonists also had weak but significant blocking action on EA-induced inhibitory effect on chronic pain. Conclusions : Dorsal hem cell responses, afferent C fiber stimulation, chronic pain, electroacupuncture, serotonergic receptors.

• Journal of Acupuncture Research
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• 제21권6호
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• pp.51-62
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• 2004

Objective: To investigate the analgesic effect and its serotonergic mechanism, especially related with 5-HTI and 5-HT2 receptor, of electroacupuncture(EA) in the rat model of collagen-induced arthritis(CIA). Methods : Immunization of male Sprague-Dawley rats with bovine type II (C II) collagen emulsified in Freund's incomplete adjuvant, followed by a booster injection 14 days later, leads to development of arthritis in more than 70% of rats by 21 days postinjection. After three weeks of first immunization, EA stimulation(2 Hz, 0.07 mA, 0.3 ms) was delivered into Jogsamni($ST_{36}$) for 30 minutes. Analgesic effect was evaluated by tail flick latency(TFL). We compared the analgesic effect of EA with TFLs between pretreatment of normal saline and pretreatment of spiroxatrine (5-HT1 receptor antagonist, 1mg/kg, intraperitoneal) and spiperone (5-HT2 receptor antagonist, 1 mg/kg, intraperitoneal) in CIA. Results : 1. TFLs were gradually decreased in CIA as increasing severity of arthritis. 2. Jogsamni($ST_{36}$) EA stimulation in CIA increased TFLs and the effect lasted for 60 minutes. 3. Increased TFLs with Jogsamni($ST_{36}$) EA stimulation were inhibited by pretreatment of spiroxatrine and spiperone in CIA. Conclusions : Jogsamni($ST_{36}$) EA showed analgesic effects in CIA The analgesic effects of Jogsamni($ST_{36}$) EA were inhibited by spiroxatrine and spiperone pretreatment. These observations suggest that 5-HT1 and 5-HT2 serotonergic receptor, which involve the release of serotonin neurotransmitter, play an important roles in analgesic mechanism of EA stimulation.

• The Korean Journal of Physiology and Pharmacology
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• 제20권4호
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• pp.407-414
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• 2016

This study was performed to investigate whether the spinal cholinergic and serotonergic analgesic systems mediate the relieving effect of electroacupuncture (EA) on oxaliplatin-induced neuropathic cold allodynia in rats. The cold allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) was evaluated by immersing the rat's tail into cold water ($4^{\circ}C$) and measuring the withdrawal latency. EA stimulation (2 Hz, 0.3-ms pulse duration, 0.2~0.3 mA) at the acupoint ST36, GV3, or LI11 all showed a significant anti-allodynic effect, which was stronger at ST36. The analgesic effect of EA at ST36 was blocked by intraperitoneal injection of muscarinic acetylcholine receptor antagonist (atropine, 1 mg/kg), but not by nicotinic (mecamylamine, 2 mg/kg) receptor antagonist. Furthermore, intrathecal administration of $M_2$ (methoctramine, $10{\mu}g$) and $M_3$ (4-DAMP, $10{\mu}g$) receptor antagonist, but not $M_1$ (pirenzepine, $10{\mu}g$) receptor antagonist, blocked the effect. Also, spinal administration of $5-HT_3$ (MDL-72222, $12{\mu}g$) receptor antagonist, but not $5-HT_{1A}$ (NAN-190, $15{\mu}g$) or $5-HT_{2A}$ (ketanserin, $30{\mu}g$) receptor antagonist, prevented the anti-allodynic effect of EA. These results suggest that EA may have a significant analgesic action against oxaliplatin-induced neuropathic pain, which is mediated by spinal cholinergic ($M_2$, $M_3$) and serotonergic ($5-HT_3$) receptors.

• 한국자원식물학회지
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• 제23권6호
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• pp.513-518
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• 2010

In the present study, the antinociceptive profiles of Dianthus chinensis L extract were examined in ICR mice. Dianthus chinensis L extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Dianthus chinensis L extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P ($0.7\;{\mu}g$) was diminished by Dianthus chinensis L extract. Intraperitoneal (i.p.) pretreatment with yohimbine ($\alpha_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Dianthus chinensis L extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Dianthus chinensis L extract in the writhing test. Our results suggest that Dianthus chinensis L extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Dianthus chinensis L extract may be mediated by $\alpha_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• 생물정신의학
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• 제11권2호
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• pp.110-116
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• 2004

Objectives:Recently, polymorphisms of several serotonin genes have been suggested to be associated with suicide, but the results are still unclear. We examined whether the T102C polymorphisms of the serotonin 2A receptor gene and the G861C polymorphisms of the serotonin 1B receptor gene were associated with suicidal behavior using drug intoxication. Methods:The subjects were 52 patients who visited emergency room with suicidal behaviors. Fifty controls were selected from healthy volunteers matched for sex and age to the suicide subjects. The polymorphisms were analyzed with TaqMan$^{(R)}$ assay using primers based on previous studies. Results:The T102C polymorphism of the serotonin 2A receptor gene showed no significant difference between the suicidal attempters and controls in both genotype and allele frequency analyses(p=0.179 and p=0.422, respectively). There was no statistically significant difference between the suicidal attempters and the controls in the G861C polymorphism of the serotonin 1B receptor gene and any significant effect of the genotype distributions or the allele frequencies was not observed(p=0.092 and p=0.987, respectively). Conclusion:These findings suggest that the T102C polymorphism in serotonin 2A receptor gene and the G861C polymorphism in serotonin 1B receptor gene are not related to the susceptibility to suicide attempts using drugs. To clarify the genetic influences of the serotonergic system on suicidal behavior, the polymorphisms of other candidate genes in the serotonergic system should be studied with larger numbers of subjects.

• The Korean Journal of Physiology and Pharmacology
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• 제24권6호
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• pp.517-527
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• 2020

Layer 2/3 pyramidal neurons (L2/3 PyNs) of the cortex extend their basal dendrites near the soma and as apical dendritic tufts in layer 1, which mainly receive feedforward and feedback inputs, respectively. It is suggested that neuromodulators such as serotonin and acetylcholine may regulate the information flow between brain structures depending on the brain state. However, little is known about the dendritic compartment-specific induction of synaptic transmission in single PyNs. Here, we studied layer-specific serotonergic and cholinergic induction of long-term synaptic plasticity in L2/3 PyNs of the agranular insular cortex, a lateral component of the orbitofrontal cortex. Using FM1-43 dye unloading, we verified that local electrical stimulation to layers 1 (L1) and 3 (L3) activated axon terminals mostly located in L1 and perisomatic area (L2/3). Independent and AMPA receptor-mediated excitatory postsynaptic potential was evoked by local electrical stimulation of either L1 or L3. Application of serotonin (5-HT, 10 μM) induced activity-dependent longterm depression (LTD) in L2/3 but not in L1 inputs. LTD induced by 5-HT was blocked by the 5-HT₂ receptor antagonist ketanserin, an NMDA receptor antagonist and by intracellular Ca²⁺ chelation. The 5-HT₂ receptor agonist α-me-5-HT mimicked the LTD induced by 5-HT. However, the application of carbachol induced muscarinic receptor-dependent LTD in both inputs. The differential layer-specific induction of LTD by neuromodulators might play an important role in information processing mechanism of the prefrontal cortex.

• 한국약용작물학회지
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• 제18권4호
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• pp.238-243
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• 2010

In the present study, the antinociceptive profiles of Viola tricolor L. (V. tricolor L.) extract were examined in ICR mice. V. tricolor L. extract administered orally (200mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, V. tricolor L. extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 ${\mu}g$) was diminished by V. tricolor L. extract. Intraperitoneal (i.p.) pretreatment with yohimbine (${\alpha}_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by V. tricolor L. extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by V. tricolor L. extract in the writhing test. Our results suggest that V. tricolor L. extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of V. tricolor L. extract may be mediated by ${\alpha}_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• The Korean Journal of Physiology and Pharmacology
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• 제16권2호
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• pp.119-123
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• 2012

In the present study, the antinociceptive profiles of $Agrimonia$ $pilosa$ $Ledeb$ extract were examined in ICR mice. $Agrimonia$ $pilosa$ $Ledeb$ extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, $Agrimonia$ $pilosa$ $Ledeb$ extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 ${\mu}g$) was diminished by $Agrimonia$ $pilosa$ $Ledeb$ extract. Intraperitoneal (i.p.) pretreatment with yohimbine (${\alpha}_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by $Agrimonia$ $pilosa$ $Ledeb$ extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by $Agrimonia$ $pilosa$ $Ledeb$ extract in the writhing test. Our results suggest that $Agrimonia$ $pilosa$ $Ledeb$ extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of $Agrimonia$ $pilosa$ $Ledeb$ extract may be mediated by ${\alpha}_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.