• 제목/요약/키워드: Serotonergic receptors.

검색결과 37건 처리시간 0.022초

뇌의 REM 수면 발생기전 (Brain Mechanisms Generating REM Sleep)

  • 손진욱
    • 수면정신생리
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    • 제2권2호
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    • pp.133-137
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    • 1995
  • The author reviews current knowledge about what REM sleep is and where and how it is generated. REM sleep is the state in which our most vivid dreams occur. REM sleep is identified by the simultaneous presence of a desynchronized cortical EEG, an absence of activity in the antigravity muscles(atonia), and periodic bursts of rapid eye movements. Another characteristic phenomena of REM sleep are the highly synchronized hippocampal EEG of theta frequency and the ponto-geniculo-occipital(PGO) spike. All these phenomena can be explained in terms of changes in neuronal activity. Transection studies have determined that the pons is sufficient for generating REM sleep. Lesion studies have identified a small region in the lateral pontine tegmentum corresponding to lateral portions of the nucleus reticularis pontis oralis(RPO) and the region immediately ventral to the locus coeruleus, which is required for REM sleep. Unit recording studies have found a population of cells within this region that is selectively active in REM sleep. Cholinergic neurons of the giant cell field of pontine tegmentum(ETG), which is 'REM a sleep-on cells', has shown to be critically involved in the generation of REM sleep. Noradrenergic neurons of the locus coeruleus and serotonergic neurons of the dorsal raphe, which are called 'REM sleep-off cells', appear to act in a reciprocal manner to the cholinergic neurons. It is proposed that the periodic cessations of discharge of 'REM sleep-off cells' during REM sleep might be significant for the prevention of the desensitization of receptors of these neurons.

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정신분열증 환자에서 Cimetidine에 의한 Prolactin 분비 반응 - 양성 및 음성 아형 남자 환자에서 - (Prolactin Response to Cimetidine in the Schizophrenics - In Unmedicated Male Positive and Negative Patients -)

  • 진혁희;권영준;정희연;한선호
    • 생물정신의학
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    • 제3권1호
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    • pp.121-126
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    • 1996
  • 최근에 정신분열증의 병태생리에 세로토닌계에 대한 관심이 고조되고 있고 cimetidine이 간접적인 세로토닌계 자극으로 PRL 분비 반응을 유발한다 하여 본 연구에서는 양성 및 음성 증상 척도 (PANSS)에 의하여 양성 및 음성 아형으로 정신분열증 환자군을 구분, 정상대조군과 두 아형들간의 PRL 기저지와 cimetidine 유발성 PRL $T_{30}$치를 측정하여 정신분열증의 아형에 따른 seretonin과의 상관 관계를 규명하고자 연구가 시도되었다. 대상은 DSM-N(APA 1994)의 진단 기준을 만족시키는 입원 당시 7일 이상 항정신병약물을 복용하지 않은 남자 정신분열증 환자 19명으로 하였고, PANSS에 의해 양성 아형 (12명) 및 음성 아형 (7명) 환자군으로 나누어 오전 9시에 PRL 기저치 측정과 함께 cimetidine(5mg/kg) 정액 점주 30분 후인 9시 30분에 cimetidine에 의한 PRL $T_{30}$치를 측정하여 다음과 같은 결과를 얻었다. 1) PRL 기저치는 세 군에서 차이가 없었다. 2) 기저와 $T_{30}$간에 PRL치의 변화는 세 군에서 증가했음을 보여주었다. 3) 기저와 $T_{30}$간에 PRL치 증가량에 대한 상대적인 비교에서 정상대조군과 양성 아형 환자군 간, 양성 아형 환자군과 음성 아형 환자군 간에는 차이가 없었으나 정상대조군과 음성 아형 환자군 간에서 상호 유의한 차이가 있었다(p<0.05). 상기 연구 결과들은 정상대조군에서 보다 음성 아형 환자군에서 cimetidine에 의한 PRL반응이 둔감하게 나타난 것을 보여준다 하겠다. 이러한 결과들은 정상대조군에서는 나타나지 않지만 남자 음성 아형 정신분열증 환자군에서 $5-HT_2$ 수용체 하향 조절을 포함하는 세로토닌계 활성 이상 소견이 나타날 수 있다는 가설(Meltzer등 1993) 들과 일치한다 하겠다.

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Systemically administered neurotensin receptor agonist produces antinociception through activation of spinally projecting serotonergic neurons in the rostral ventromedial medulla

  • Li, Yaqun;Kang, Dong Ho;Kim, Woong Mo;Lee, Hyung Gon;Kim, Seung Hoon;You, Hyun Eung;Choi, Jeong Il;Yoon, Myung Ha
    • The Korean Journal of Pain
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    • 제34권1호
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    • pp.58-65
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    • 2021
  • Background: Supraspinal delivery of neurotensin (NTS), which may contribute to the effect of a systemically administered agonist, has been reported to be either pronociceptive or antinociceptive. Here, we evaluated the effects of systemically administered NTSR1 agonist in a rat model of neuropathic pain and elucidated the underlying supraspinal mechanism. Methods: Neuropathic pain was induced by L5 and L6 spinal nerve ligation in male Sprague-Dawley rats. The effects of intraperitoneally administered NTSR1 agonist PD 149163 was assessed using von Frey filaments. To examine the role of 5-HT neurotransmission, a serotonin (5-HT) receptor antagonist dihydroergocristine was pretreated intrathecally, and spinal microdialysis studies were performed to measure the change in extracellular level of 5-HT in response to PD 149163 administration. To investigate the supraspinal mechanism, NTSR1 antagonist 48692 was microinjected into the rostral ventromedial medulla (RVM) prior to systemic PD 149163. Additionally, the effect of intrathecal DHE on intra-RVM PD 149163 was assessed. Results: Intraperitoneally administered PD 149163 exhibited a dose-dependent attenuation of mechanical allodynia. This effect was partially reversed by intrathecal pretreatment with dihydroergocristine and was accompanied by an increased extracellular level of 5-HT in the spinal cord. The PD 149163-produced antinociception was also blocked by intra-RVM SB 48692. Direct injection of PD 149163 into the RVM mimicked the maximum effect of the same drug delivered intraperitoneally, which was reversed by intrathecal dihydroergocristine. Conclusions: These observations indicate that systemically administered NTSR1 agonist produces antinociception through the NTSR1 in the RVM, activating descending serotonergic projection to release 5-HT into the spinal dorsal horn.

정신분열병환자에서 만발성 운동장애와 $5-HT_6$ 수용체 유전자 다형성(267C/T)과의 관계 (Association between Tardive Dyskinesia and 267C/T Polymorphism of $5-HT_6$ Receptor Gene in Schizophrenia)

  • 한상우;김동현;전용호
    • 생물정신의학
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    • 제11권1호
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    • pp.54-60
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    • 2004
  • Objectives:Tardive dyskinesia(TD) is a serious side effect associated with long-term antipsychotic treatments. Some candidate genetic polymorphisms were reported to be associated with TD and possible involvement of serotonergic receptors in the pathophysiology of TD has been suggested. In the present study, we investigated the association between $5-HT_6$ receptor gene polymorphism and TD with schizophrenia. Methods:To investigate the relationship between $5-HT_6$ receptor gene polymorphism and TD, 60 patients with TD were compared with 60 patients without TD. The 267C/T allele of $5-HT_6$ receptor gene was genotyped by means of polymerase chain reaction method. TD was evaluated using the Abnormal Involuntary Movement Scale(AIMS). Results:The patients with the three 267C/T genotype showed no significant differences in age, gender, and duration of illness. No significant difference in genotype frequencies was observed between schizophrenic patients with and without TD. In addition, there was no difference in allele frequencies. Further analysis with an measure of AIMS scores showed that these scores were not significantly influenced by the $5-HT_6$ receptor gene polymorphism. Conclusion:These results suggest that 267C/T polymorphism of $5-HT_6$ receptor gene is not significantly associated with susceptibility to TD in schizophrenia.

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리스페리돈이 심혈관계에 미치는 영향 (The Cardiovascular Effect of Risperidone)

  • 최세진;전진숙;최영태
    • 생물정신의학
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    • 제7권2호
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    • pp.191-197
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    • 2000
  • Objectives : Risperidone is a new antipsychotic drug developed to overcome the therapeutic limitation of conventional antipsychotics. It responses to negative as well as positive symptoms by blocking both dopaminergic and serotonergic receptors, causing no significant side effects such as agranulocytosis and seizure. It is, however, not known whether it induces any serious cardiovascular side effects as evoked by other conventional antipsychotic drugs. The aims of this study were to evaluate the effect of risperidone on cardiovascular function, and to discuss the factors affecting the cardiovascular function. Methods : For 42 patients(22 males and 20 females) diagnosed as schizophrenia, schizophreniform disorder or schizoaffective disorder according to the DSM-IV classification, the cardiovascular fuctions such as heart rate, systolic and diastolic blood pressure, PR interval, QRS interval and QT interval were successively checked before and after 2 weeks and 4 weeks risperidone administration. Furthermore, variables such as body weight, Brief Psychiatric Rating Scale(BPRS), Clinical Global Impression(CGI), Extrapyramidal Symptom Rating Scale(ESRS), Anticholinergic Rating Scale(ARS), serum cholesterol level, serum triglyceride level, serum high-density-lipoprotein level, serum WBC, serum Hb, serum platelet level, prothrombin time and partial thromboplastin time were also analyzed before and after 2 weeks and 4 weeks risperidone administration. Results : 1) Risperidone treatment resulted in a significantly decreased heart rate and increased QT interval after 4 weeks administration(p<0.005 respectively). 2) The scores of BPRS and CGI were significantly decreased after 2 weeks and 4 weeks risperidone administration as compared with baseline(p<0.001 respectively). The scores of ESRS and ASRS were significantly increased after 2 weeks and 4 weeks risperidone administration as compared with baseline(p<0.001 respectively). 3) There were positive correlations between heart rate after 4 weeks and total dose(P<0.05). Blood pressure was significantly(p<0.05) correlated with sex(higher in male) and significantly(p<0.05) positive correlated with body weight. QT interval was significantly(p<0.05) correlated with sex(longer in female) and smoking history(shorter in smokers). Conclusions : Risperidone could induce significant change in heart rate and Q-T interval. Therefore, the cardiovascular safety for risperidone should be reconsidered according to the duration and dosage increase.

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Antinociceptive and anti-inflammatory effects of ginsenoside Rf in a rat model of incisional pain

  • Kim, Min Kyoung;Kang, Hyun;Baek, Chong Wha;Jung, Yong Hun;Woo, Young Cheol;Choi, Geun Joo;Shin, Hwa Yong;Kim, Kyung Soo
    • Journal of Ginseng Research
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    • 제42권2호
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    • pp.183-191
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    • 2018
  • Background: Ginseng saponin has long been used as a traditional Asian medicine and is known to be effective in treating various kinds of pain. Ginsenoside Rf is one of the biologically active saponins found in ginseng. We evaluated ginsenoside Rf's antinociceptive and anti-inflammatory effects, and its mechanism of action on adrenergic and serotonergic receptors, in an incisional pain model. Methods: Mechanical hyperalgesia was induced via plantar incision in rats followed by intraperitoneal administration of increasing doses of ginsenoside Rf (vehicle, 0.5 mg/kg, 1 mg/kg, 1.5 mg/kg, and 2 mg/kg). The antinociceptive effect was also compared in a Positive Control Group that received a ketorolac (30 mg/kg) injection, and the $Na{\ddot{i}}ve$ Group, which did not undergo incision. To evaluate the mechanism of action, rats were treated with prazosin (1 mg/kg), yohimbine (2 mg/kg), or ketanserin (1 mg/kg) prior to receiving ginsenoside Rf (1.5 mg/kg). The mechanical withdrawal threshold was measured using von Frey filaments at various time points before and after ginsenoside Rf administration. To evaluate the anti-inflammatory effect, serum interleukin $(IL)-1{\beta}$, IL-6, and tumor necrotizing $factor-{\alpha}$ levels were measured. Results: Ginsenoside Rf increased the mechanical withdrawal threshold significantly, with a curvilinear dose-response curve peaking at 1.5 mg/kg. $IL-1{\beta}$, IL-6, and tumor necrotizing $factor-{\alpha}$ levels significantly decreased after ginsenoside Rf treatment. Ginsenoside Rf's antinociceptive effect was reduced by yohimbine, but potentiated by prazosin and ketanserin. Conclusion: Intraperitoneal ginsenoside Rf has an antinociceptive effect peaking at a dose of 1.5 mg/kg. Anti-inflammatory effects were also detected.

Risperidone이 혈청 Prolactin 농도에 미치는 영향 (The Effect of Risperidone on Serum Prolactin Concentrations)

  • 전진숙;조웅;오병훈
    • 생물정신의학
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    • 제5권2호
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    • pp.253-262
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    • 1998
  • Objectives : Risperidone, an atypical antipsychitics which blocks both dopaminergic and serotonergic receptors, have a good response to the negative symptoms as well as positive symptoms, and improve cognitive dysfunction of schizophrenic patients. Furthermore, it has few extrapyramidal side effects and tardive dyskinesia. Although it had been reported that the atypical antipsychotics have less effect on prolactin(PRL) than the classical antipsychotics, we could experience PRL-associated symptoms such as amenorrhea, galactorrhea and hyperprolactinemia in practice. Therefore, we tried to identify the sex differences of risperidone-induced hyperprolactinemia, to evaluate factors affecting PRL levels, and to know the association between cognitive disorders and PRL. Methods : The baseline levels of PRL and TSH prior to risperidone administration were measured by enzyme immunoassay method for 50 patients(25 ma-les and 25 females) admitted with schizophrenia, schizoaffective disorder or schizophreniform disorder according to the DSM-IV classification, and the measurements of PRL were repeated on the 2nd and the 4th wks of risperidone administration. Concomitantly, the severity of psychotic symptoms using CGI, BPRS and PANSS, and the cognitive dysfunction using PANSS-CF were assessed prior to, on the 2nd and the 4th wks of risperidone administration. The PRL and TSH levels of 54 healthy controls(29 males and 25 females) who had no medical, neurological and psychiatric illnesses were also evaluated. Furthermore, the correlation with the psychiatric diagnosis, education, age, sex, duration of illnesses, risperidone dosage, duration of risperdone administration, TSH concentration, cognitive function, severity of psychotic symptoms were also identified. Results : 1) The baseline PRL levels of female schizophrenics($74.3{\pm}49.6ng/ml$) were significantly(p<0.005) higher than those of males($36.3{\pm}24.6ng/ml$), which were significantly(p<0.0001 respectively) higher than those of controls(females $16.9{\pm}6.1ng/ml$, males $13.3{\pm}4.9ng/ml$). The PRL levels measured on the 2nd wks(females $133.7{\pm}47.8ng/ml$, males $56.9{\pm}23.6ng/ml$) and on the 4th wks(females $146.1{\pm}45.9ng/ml$, males $70.0{\pm}31.5ng/ml$) after risperidone administration were significantly(p<0.0001 respectively) higher in females. The mean dosages of risperidone on the 2nd wks were $3.8{\pm}1.7mg$(2-6mg) for the females and $4.0{\pm}1.6mg$(2-6mg) for the males, and on the 4th wks were $4.5{\pm}2.1mg$(2-8mg) for the females and $5.4{\pm}2.2mg$(2-8mg) for the males. 2) The rise of PRL levels were positively correlated with increased risperidone dosage in males(${\gamma}$=0.307 on the 2nd wks and ${\gamma}$=0.280 on the 4th wks), while they were not correlated with dosages in females. For the females, the PRL levels were negatively correlated(${\gamma}$=-0.320) with decrease of TSH concentration. The baseline PRL levels were not correlated with age, education, duration of illnesses, psychopathology, cognitive disorders in both males and females, while it was negatively correlated with TSH levels only in females(${\gamma}$=-0.320). 3) The cognitive dysfunction was not correlated with PRL levels in males, while PANSS-CF scores were negatively correlated with PRL levels(${\gamma}$=-0.220 on the 2nd wks and ${\gamma}$=-0.366 on the 4th wks) in females. The psychopathology was positively correlated with cognitive dysfunction in both males and females. Therefore, the risperidone-induced cognitive improvement seemed to be correlated with improvement of psychopathology in both males and females, and with increase in PRL levels only in females. Conclusions : The fact that the serum PRL levels of schizophrenics were higher than those of controls, especially in females suggested that it could be related with risperidone dosage in males and with primary pathological process in females. The risperidone-associated cognitive improvement seemed to be related with general improvement of psychopathology as well as the rise of PRL levels especially in females. The facts that the effect of risperidoneinduced hyperprolactinemia and the cognitive function were more in females suggested that somewhat different mechanisms could be exerted on them.

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