본문 바로가기
KERD
논문KCI 등재

흰쥐에서 출생 전의 Nitric Oxide Synthase 억제제의 노출이 출생 후의 MK-801에 의해 유도된 행동 민감성에 미치는 영향

Effects of Prenatal Exposure to Nitric Oxide Synthase Inhibitor on MK-801-Elicited Behavioral Sensitivity in Postnatal Rats

정영인|김길중|박숙현
대한신경정신의학회 (Korean Neuropsychiatric Association)|2007.01|신경정신의학 (JOURNAL OF THE KOREAN NEUROPSYCHIATRIC ASSOCIATION)|제46권 제1호|pp. 13-18

1

조회

0

다운로드

1

인용

0

참고문헌

키워드

Nitric oxide(NO)·Nitric oxide synthase 억제·MK-801.Nitric oxide (NO)· Nitric oxide synthase inhibitor· MK-801.
주제분류정신과학

초록

목 적 본 연구는 신경세포의 성장과 이동에 영향을 미치는 NOS 억제제를 임신 중에 투여 받은 어미 쥐에서 태어난 쥐를 대상으로, NMDA 수용체의 비경쟁적 길항제인 MK-801에 의한 운동 활성의 변화를 알아보고, 항정신병약물이 MK-801에 의해 유도된 행동 변화에 미치는 영향을 평가하여, 신경발달학적 측면에서 정신분열병의 병인을 구명해보고자 함이 본 연구의 목적이다. 방 법 체중 200~250 gm의 암컷과 수컷 Sprague-Dawley계 흰쥐를 같은 사육상자 내에서 물과 사료를 자유로이 섭취하게 하면서 임신을 유도하였다. 임신 후기의 어미 쥐를 세군으로 나누고 제 1 실험군에는 Nω-nitro-L-arginine (L-NA) 25 mg, 제 2 실험군에는 L-NA 40 mg을, 세번째 대조군에는 생리적 식염수를 투여하였다. 생후 5주째에 MK-801을 복강 내로 1회 투여해서 대조군과 실험군 간에 있어서 약물의 감수성의 차이를 Neurovision analysis라는 자동분석프로그램을 이용해서 행동 변화를 평가하였다. 다음으로 각 군에 haloperidol과 clozapine을 전처치하고 10분 후에 MK-801을 투여하고 행동 변화를 측정하여 MK-801 감수성에 미치는 효과의 차이를 확인하였다.

Abstract

Objectives：The aim of the present study was to investigate the role of prenatal exposure to NOS (nitric oxide synthase) inhibitor during the 3rd trimester of pregnancy on MK-801-elicited behavioral sensitivity in postnatal juvenile rats and the effect of an antipsychotic drug on the change in MK-801-elicited behavioral sensitivity in an attempt to elucidate the participation of NO (nitric oxide) in the pathophysiology of schizophrenia. Methods：L-NA (N-nitro-L-arginine, 25 mg/kg, 40 mg/kg) was injected intraperitoneally in pregnant Sprague-Dawley rats during the 3rd trimester of pregrancy. On postnatal day 35, MK-801-elicited behavioral sensitivity was measured using Neurovision Analysis (automatic motor analysis program). Animals were pretreated with haloperidol or clozapine as a antipsychotic drug before administration of MK-801. Statistical tests of drug effects were performed using ANOVA. A value producing p<0.05 was considered to be significant. Results：MK-801-elicited locomotor activity was significantly increased with prenatal exposure to L-NA in postnatal rats. The change in MK-801-elicited behavioral sensitivity was significantly diminished by pretreatment with haloperidol and clozapine. Conclusion：These findings suggest that NO may in part play an important role in neurodevelopment in that prenatal exposure to NOS inhibitor can influence MK-801-elicited behavioral sensitivity in postnatal rats. These results also indicate that the neurodevelopmental abnormality may predispose schizophrenia. (J Korean Neuropsychiatr Assoc 2007;46(1):13-18)

참고문헌 (32)

  1. Garthwaite J, "nitric oxide and cell-cell signalling in the nervous system", pp.60~67
  2. Butler AR, "The physiological role of nitric oxide", pp.233~241
  3. Snyder SH, "Biological roles of nitric oxide", pp.68~77
  4. Hirsch DB, "Neurotransmitter release regulated by nitric oxide in PC-12 cells and brain synaptosomes", pp.749~754
  5. dopamine release from striatal slices, , 35192~198
  6. "Nitric oxide increases dopamine and serotonin release in the medial preoptic area", pp.87~89
  7. Dawson TM, "Gases as biological mesengers nitric oxide and carbon monoxide in the brain", pp.5147~5159
  8. Lipton SA, "A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds", pp.626~632
  9. Gally JA, "posible efects of a short-lived rapidly difusible signal in the NOS 억제의 출생 전 투여와 MK-801에 의한 행동 변화와의 관계 S 2007 18 development and function of the nervous system", pp.3547~3551
  10. Hess DT, "Neuronal growth cone collapse and inhibition of protein fatty acylation by nitric oxide", pp.562~565
  11. Ogilvie P, "Induction and variants of neuronal nitric oxide synthase type I during synaptogenesis.", 9, pp.799~806 (1995)
  12. Garthwaite J, "Endothelium-derived relaxing factor release on activation of NMDA receptors sugests role as intercellular mesenger in the brain", pp.385~387
  13. Bunney WE Jr, "Altered distribution of nicotinamide-adenine dinucl-eotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbances of cortical development", pp.169~17
  14. Vinuela A, "Distorted distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase neurons in temporal lobe of schizophrenics implies ano-malous cortical development", pp.178~187
  15. Das I, "Elevated platelet calcium mobilization and nitric oxide synthase acti-vity may reflect abnormalities in schizophrenic brain.", 212, pp.375~380 (1995)
  16. Das I, "Circulating L-arginine metabolites and platelet nitric oxide synthase in schizophrenics.", 15, pp.55~ (1995)
  17. Khan NS, "Presence of a nitric oxide synthase inhibitor in schizophrenic subjects plasma.", 15, pp.62~63 (1995)
  18. Das I, "Elevated endogenous nitric oxide synthase inhibitor in schizophrenic plasma may reflect abnor-malities in brain nitric oxide production.", 215, pp.209~211 (1996)
  19. Biedermann J, "The brainstem reticular formation in schizophrenia", pp.31~48
  20. Taraska T, "Nitric oxide and the neurotoxic effects of methamphetamine and 3,4-methylenedioxymethamphetamine.", 280, pp.941~947 (1997)
  21. Hu J, "Inhibition of neuronal nitric oxide synthase by antipsychotic drugs", pp.161~166
  22. Deutsch SI, "7-Nitroindazole and methylene blue, inhibitors of neuronal nitric oxide synthase and NO-stimulated guanylate cyclase, block MK-801-elicited behaviors in mice.", 15, pp.37~43 (1996)
  23. Wiley JL, "Nitric oxide synthase inhibitors attenuate phencyclidine-induced disruption of prepulse inhibition.", 19, pp.86~94 (1998)
  24. Johanson C, "Nitric oxide synthase inhi-bition blocks phencyclidine-induced behavioural effects on prepulse inhibition and locomotor activity in the rat.", 131, pp.167~173 (1997)
  25. Hirsch SR, "A pivotal role for gluta-mate in the pathogenesis of schizophrenia", pp.797~802
  26. Carlsson A, "A glutamatergic deficiency model of schizophrenia.", 174, pp.2~6 (1997)
  27. Lahti AC, "Taminga CA. Subanesthetic doses of ketamine stimulate psychosis in schizophrenia.", 13, pp.9~19 (1995)
  28. Steinpresis RE, "The behavioural and neurochemical effects of phen-cyclidine in humans and animals: some implications for medelling psychosis.", 74, pp.45~55 (1996)
  29. Kim JS, "Low cere-brospinal fluid glutamate in schizophrenic patients and a new hypo-thesis on schizophrenia", pp.379~382
  30. Stahl SM, "Esential psychopharmacology: neuroscientific basis and practical applications.", pp.365~399 (2000), Cam-bridge University Pres, Cambridge, UK
  31. Mallard EC, "Ventriculomegaly and reduced hippocampal volume following intrauterine growth-res-triction: implication for the aetiology of schizophrenia.", 40, pp.11~21 (1999)
  32. Deutsch SI, "Measurement of an explosive behavior in the mouse induced by MK-801", pp.251~257

관련 논문AI추천

흰쥐에서 출생 전 Nitric Oxide Synthase 억제제의 노출이 출생 후 강제 수영 시의 행동 변화에 미치는 영향김길중, 박숙현, 정영인대한신경정신의학회 · 신경정신의학2007 · 제46권 제5호Differential Effects of Olanzapine and Haloperidol on MK-801-induced Memory Impairment in Mice김영훈, 박성우, 서미경, 송재천, 이정구대한정신약물학회 · Clinical Psychopharmacology and Neuroscience2016 · 제14권 제3호Effects of Tianeptine on Adult Rats Following Prenatal Stress이화영, Hak-Jae Kim, Hyung-Ki Kim, Ik-Hyun Cho, Jonghoon Seo, Jun-Tack Kwon, Sanghyun Lee, Young-Ock Kim대한정신약물학회 · Clinical Psychopharmacology and Neuroscience2018 · 제16권 제2호Effect Neonatal Ketamine Treatment on Exploratory and Anxiety-like Behaviours in AdulthoodKübra Akillioglu, Mustafa Karadepe대한정신약물학회 · Clinical Psychopharmacology and Neuroscience2021 · 제19권 제1호Electroencephalographic Power Spectral Profile in a Rat Model of Schizophrenia이만기, Hwan Soo Jang, Hyeon Ryeol Jo, Hyo Soon Choi, Jae Hyun Lim, Jong Ho Kim대한정신약물학회 · Clinical Psychopharmacology and Neuroscience2009 · 제7권 제1호Effects of Quetiapine on Dizocilpine-induced Prepulse Inhibition Deficits in Mice: Possible Role of the aα1 Adrenergic Receptor갠지하시모토, Mao Horio, Masaomi Iyo, Yuko Fujita, Yuko Tanibuchi대한정신약물학회 · Clinical Psychopharmacology and Neuroscience2010 · 제8권 제3호

이 간행물의 다른 논문 (12건)

2007 World Psychiatric Association Regional Meeting 을 준비하며권준수pp. 3-4한국인 알코올 의존 자녀들과 도파민 D2, D4 수용체, GABAA 수용체 β Subunit 및 세로토닌 운반체 유전자 다형성 사이의 연관성에 대한 예비적 연구남궁기, 전진용, 천근아, 김재원, 이준영pp. 5-12정신분열병의 임상적 고위험군의 특징 : '서울청년클리닉'의 자연 추적 관찰 에비연구송지연, 권준수, 하태현, 이승재, 이경진, 김성년, 이애라, 위휘, 강도형, 유소영pp. 19-28내인성 혈장 리튬 농도와 정신분열병이병학, 김성재, 윤재항, 오채근, 김종인, 김창현pp. 29-34대학생들의 자살관련행동에 관한 연구노명선, 이효정, 한성구, 이해우, 함봉진, 전홍진pp. 35-40
원문 보기