• 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.

• 대한핵의학회지
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• 제31권1호
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• pp.9-18
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• 1997

목 적 : 본 연구에서는 정량적 자가방사선사진법을 이용하여 비정형 항정신병 약물의 하나인 risperidone 이 백서 뇌의 신경수용체에 어떻게 작용하는지를 알아보고자 하였다. 대상 및 방법 : 급성투여군은 백서 30마리를 6군으로 나누어 0, 0.1, 0.25, 0.5, 1, 2mg/kg의 risperidone을 복강내 투여하고 2시간후에 단두하였고, 만성투여군은 0, 0.1, 1mg/kg의 risperidone을 21일간 복강내 투여후 단두하여 정량적자가 방사선사진법으로 $5-HT_2$과 $D_2$ 수용체에 대한 [$^3H$]spiperone 결합을 측정함으로써, 선조체, 측좌핵, 전두엽피질 각각의 $5-HT_2$과 $D_2$ 수용체의 분포변화를 측정하고 투여량에 따른 수용체의 영향을 ANOVA 검정으로 분석하였다. 결 과 : 급성투여군에서 $5-HT_2$ 수용체는 전두엽 피질에서 risperidone 투여후 0.1-2mg/kg의 투여 범위전체에서 [$^3H$]spiperone 결합이 대조군에 비하여 32% 이하로 감소하여 통계적으로 유의한 차이를 보였으며, 선조체와 측좌핵의 피질하 수용체에서는 거의 결합을 보이지 않았다. $D_2$ 수용체는 risperidone 투여량의 증가에 따라 선조체와 측좌핵의 [$^3H$]spiperone 결합이 감소하였으며, 1-2mg/kg의 투여량을 준 경우에는 대조군에 비해 57% 이하로 감소하여 통계적으로 유의한 차이를 보였다. 만성투여군에서는 피질의 $5-HT_2$ 수용체가 대조군에 비하여 저용량투여군과 고용량투여군에서 각각 51%와 46%로 감소하였다. 결론 : Risperidone은 $D_2$ 수용체를 약하게 차단하며 $D_2$ 수용체에 영향을 주는 양보다 적은 양을 투여해도 $5-HT_2$ 수용체를 차단하는 효과를 보임으로써 $5-HT_2$ 수용체에 강력히 작용하는 비정형 항정신병 약물임을 알 수 있었다.

• 분석과학
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• 제13권5호
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• pp.630-635
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• 2000

전기화학검출기를 이용한 HPLC법으로 흰쥐의 뇌 부위별 신경전달물질의 함량을 측정하였고 이것을 이용하여 뇌기능 개선에 빈용되는 원지, 육두구, 산조인, 석창포, 상기생, 맥문동, 몰약의 메탄올 추출물이 에탄올 투여 흰쥐의 뇌 부위별 신경전달 물질의 함량변화에 미치는 영향을 검토하였다. 에탄올 투여에 의해 전피질의 dopamine (DA), 3,4-dihydroxyphenyl acetic acid (DOPAC) 및 serotonin (5-HT) 함량이, 해마의 5-HT 함량이 각각 생리식염수 투여군에 비해 증가하였고, 전피질의 ${\gamma}$-aminobutyric acid(GABA) 함량은 생리식염수 투여군에 비해 감소하였다. 에탄올 투여 흰쥐의 선조체와 전피질의 DA 함량은 생약 추출물의 투여로 증가되는 경향을 보였다. 특히, 몰약 및 상기생은 에탄을 투여 휜쥐의 전피질에서 DA함량은 유의적으로 증가시키는 반면, 5-HT 함량은 유의적으로 감소시키는 것으로 나타났다. 몰약, 육두구, 상기생은 에탄올 투여 흰쥐의 선조체에서 GABA 함량을 유의적으로 감소시켰다. 이러한 결과는 실험에 사용된 생약 추출물의 작용이 에탄올 투여 흰쥐에서 뇌 부위 및 신경전달물질에 대해 선택적으로 나타나고 있음을 보여준다.

• 수면정신생리
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• 제20권1호
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• pp.5-9
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• 2013

One of hypothesis is that sleep loss related to a decrease in serotonergic activity plays a significant role in attempted suicide. A growing evidence suggests that central serotonergic activity plays a key role in the etiology of suicide. It has been reported that the cerebrospinal fluid (CSF) levels of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of serotonin, were reduced in suicide attempters. In addition, there is evidence that tryptophan hydroxylase is associated with suicide. The association between sleep and suicide was also suggested by some researchers. Several recent studies have showed the association between sleep disturbance and suicide rates in patients with mental disorders and in a general population. In addition, it has been suggested that serotonin plays a role in maintaining arousal and regulating muscle tone and in regulating some of the phasic events of REM sleep. Especially, it is well-known that 5-HT2 receptors are related to slow wave sleep. In conclusion, it is clear that sleep, serotonin activity, and suicide are linked, although the direction of causation needs clarification. In future, large population-based cohort studies are needed to demonstrate the direction of causation in the relationships between sleep, serotonin activity, and suicide.

• Biomolecules & Therapeutics
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• 제9권2호
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• pp.88-95
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• 2001

(+)-Methamphetamine (METH) is a psychostimulant, which has been the most popular abused drug in Korea. The rewarding mechanism in METH abuse has been reported to be mediated by dopaminergic system. Recently, it has been reported that dopamine releaser (phentermine) plays a dominant role in the discriminative stimulus effects of METH, whereas 5-HT releaser (fenfluramine) can strongly modify METH self-administration. The present study is designed to assess the behavioral changes and the changes of the serotonin receptors in the brains of rats administered repeated of self-administered METH. The repeated administration of 1.0 mg/kg/day METH for 12 days increased locomotor activities, and there was no difference between i.v. and i.p. treatment. Rats had actively acquired METH self-administration for 3 weeks at 0.1 or 0.2 mg/kg/injection. Whereas, it was taken few days to acquire sucrose pellet self-administration. The binding of [$^3$H]-8-hydroxy-DPAT (5-H $T_{1A}$ receptors) and [$^3$H]-5-carboxytryptamine (5-H $T_{1B}$ receptors) to brain sections was examined. Both passive administration and self-administration of METH did not change significantly the serotonin receptors levels in hippocampus, striatum and nucleus accumbens. These results suggest that serotonin receptors may not change in the acquisition period of METH self-administration, and we are trying to investigate the serotonin receptors levels of brain in rats maintained of METH self-administration.n.n.

• Bulletin of the Korean Chemical Society
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• 제30권8호
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• pp.1873-1876
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• 2009

• 동의생리병리학회지
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• 제32권4호
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• pp.247-254
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• 2018

A This study evaluated the antidepressant effects of the herbal mixture CPAE(Cynanchum wilfordii Hemsley, Phlomis umbrosa Turcz, and Angelica gigas Nakai) using several tests, including a test for serotonin 6($5-HT_6$) receptor activity, the forced swimming test(FST), and tests for corticosterone(CORT) and monoamine levels. CPAE showed antagonistic effects on the $5-HT_6$ receptor in a stable $5-HT_6$ receptor-expressing cell line. We subsequently confirmed the antidepressant effects of CPAE in chronic stress model in mice and explored the underlying mechanisms of its action. Specifically, we observed that CPAE treatment significantly reduced immobility time in the FST and effectively restored abnormal levels of CORT in plasma and of monoamines(serotonin, dopamine, and norepinephrine) in hippocampus and prefrontal cortex. These results suggest that CPAE has significant antidepressant effects.

• Journal of Ginseng Research
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• 제16권3호
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• pp.183-189
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• 1992

Effect of the standardized ginseng extract(G115) on the central monoaminergic systems were investigated in comparison with that of halcperidol in rats. Immediately after sacrificed by decapitation, the strlata and frontal cortex were removerl. Concentations of the monoamines dopamine and serctorLin and their metabolites were deterinintd by HPLC-EC. G115 increased the concentration of 5-HIAA and DOPAC/UA ratio in striatum. However, dopaminrrgic neuronal activities were not affected by G115 that decreased the concentratio,Is of 5-HT and 5-HIAA in frontal cortex. G115 in combination with apomorphine significantly irlcreased the concentration of DA and S-HT but decreased the DO PAC/DA ratio and 5-HIAA/5-HT ratio only in frontal cortex. These results suggest that G115 like HPD inhibits the activity of nigrostriatal dopamine neuron in striatum. However, unlike HPD it activates central monoaminergic neuron activity in frontal cortex.

• 생물정신의학
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• 제4권2호
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• pp.188-193
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• 1997

Along with psychosocial factors of suicide, biological backgrounds of suicide are explored by extensive works mostly on biological markers, neurobiological models, genetic bases, and relationships with aggression and violence. The biology of suicide confers on neurotransmitters in central nervous system exploring metabolites, receptor binding affinities, neuroendocrine challenge tests in brain, cerebrospinal fluid, blood and etc. The major concerns with suicide are focused mainly on serotonin system : low CSF 5-HIAA concentration, higher $5-HT_2$ receptor binding, and blunt prolactin response to fenfluramine. Postmortem study, in vivo study, genetic contributions, and some other issues such as suicidal methods, serum cholesterol, alcohol, and selective serotonin reuptake inhibitors are reviewed and discussed.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2002년도 창립10주년기념 및 국립독성연구원 의약품동등성평가부서 신설기념 국재학술대회:생물학적 동등성과 의약품 개발 전략을 위한 국제심포지움
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• pp.224-224
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• 2002