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研究生:楊思源
研究生(外文):Sze-Yuan Yang
論文名稱:探討多巴胺神經與正腎上腺素神經在內前額皮質區的交互作用
論文名稱(外文):The Interaction between Dopaminergic and Noradrenergic Neurons in the Medial Prefrontal Cortex
指導教授:潘懷宗潘懷宗引用關係
指導教授(外文):Wynn H. T. Pan
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:藥理學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:1999
畢業學年度:87
語文別:中文
論文頁數:85
中文關鍵詞:微量透析
外文關鍵詞:microdialysisprazosinSCH23390piperoxaneticlopride
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內前額皮質區 ( medial prefrontal cortex ; mPFC ) 同時受到由藍班核 ( Locus coruleus ; LC ) 所投射而來的正腎上腺素神經與由中腦腹側被蓋區 ( ventral tegmental area ; VTA ) 所投射而來的多巴胺神經所調控,越來越多的證據指出在這個區域中正腎上腺素神經與多巴胺神經有交互作用存在。
在實驗一及實驗二中發現:當我們利用活體內微透析的技術灌流 90 nM、150 nM、300 nM 的正腎上腺素 ( norepinephrine; NE ) 於水合三氯乙醛麻醉狀態下大白鼠的 mPFC 後,發現細胞外液中多巴胺 ( dopamine; DA ) 有明顯上升的情況 ( 110±2%、160±4%、183±6% ) ,而且灌流 NE 的濃度越高時,影響 DA 的變化程度也越大,並且具有劑量相關性。 其次,當先灌流 a1 receptor antagonist prazosin (10 mM ) 後,mPFC 的 DA 的基線濃度沒有顯著的變化,再共同灌流 300 nM NE 及 prazosin 後,會使得單獨灌流 300 nM NE 所引起多巴胺濃度上升的情形消失。 但 co-infusion a2 receptor antagonist piperoxan ( 100 mM ) 則無此阻斷作用。
在實驗三中,我們首先在 mPFC 單獨灌流正腎上腺素回收抑制劑 dispramine ( DMI ; 1 mM ) 後發現,不僅是 NE 濃度會上升 ( 194±9% ),甚至連 DA 濃度都有上升的情形 ( 158±5% )。 又依據實驗一及實驗二的結果,我們於是在 mPFC 先灌流 a1 antagonist ( prazosin ) 後,再共同灌流 prazosin 及 1 mM DMI ,偵測 mPFC 中 DA 濃度的變化情形。 實驗結果顯示:單獨灌流 10 mM prazosin 時,mPFC 的 DA 的基線濃度沒有顯著的變化,但當共同灌流 10 mM prazosin 及 1 mM DMI 後,mPFC 的 DA 濃度依舊會上升 ( 125±5% ),但程度上卻比單獨灌流 1 mM DMI 時 ( 158±5% ) 為小。
在實驗四及實驗五裡,我們在 mPFC 灌流 12 nM 、20 nM、40 nM DA 後,NE 的濃度會明顯上升到 119±3%、135±6% 及 160±6% ,顯示出當灌流的多巴胺濃度越高時,細胞外液中的正腎上腺素濃度也隨之上升得越高,兩者間具有劑量相關性。 其次,我們在 mPFC 單獨灌流 D1 antagonist- 10 nM SCH 23390 後,不會改變 NE 的基線濃度,但當共同灌流 10 nM SCH 23390 及 40 nM DA 後,會使得單獨灌流 40 nM DA 所造成的 NE 濃度上升的反應消失了,另一方面,共同灌流 DA 及 D2 receptor antagonist eticlopride ( 1 nM ) 則無此阻斷作用。
根據以上的實驗,我們得到以下的結論:在 mPFC 中,正腎上腺素神經與多巴胺神經確實有交互作用存在。 這樣的交互作用包含了: (1) 在 mPFC 中,當正腎上腺素濃度上升時,多巴胺濃度也會增加。 其中的機轉,除了是前人 ( Gresch et al., 1995 ) 所證實是兩者競爭回收載體 ( transporters ) 的結果之外,由我們的實驗結果也證實了:正腎上腺素亦會經由 a1 receptors 使得多巴胺濃度上升。 綜合以上證據我們可知:mPFC 中,正腎上腺素神經對多巴胺濃度的調控是 heterotransporter 與 heteroreceptor regulation 兩者同時存在的。 (2) 另一方面,當多巴胺濃度增加時,正腎上腺素濃度也會上升。 我們的實驗結果證實了:多巴胺濃度增加時會經由 D1 receptors 使得正腎上腺素濃度上升。 由於前人 ( Gresch et al., 1995 ) 的實驗已證明:阻斷多巴胺的回收載體 ( transporters ) 並不會影響 mPFC 的多巴胺生理濃度。 所以綜合以上結果可知:在 mPFC 中,多巴胺神經對正腎上腺素濃度調控的機轉中只有 heteroreceptor regulation 參與,而和 heterotransporter regulation 無關。

Noradrenergic and dopaminergic projections converge in the medial prefrontal cortex (mPFC) and there is growing evidence of an interaction between dopamine (DA) and norepinephrine (NE).
In our study, local infusion of NE (90 nM、150 nM and 300 nM) into the mPFC concentration-dependently increased extracellular DA (110±2%、160±4% and 183±6%) in chloral hydrate anaesthetized rats. The a1 receptor antagonist prazosin (10 mM) could block the 300 nM NE-induced increase of DA in the mPFC; but not the 2 receptor antagonist, piperoxan (100 mM). Local application of NE uptake inhibitor, desipramine (DMI; 1 mM), into the mPFC increased extracellular DA (158±5%) as well as NE (194±9%) in this area. Co-infusion of DMI and the a1 receptor antagonist prazosin (10 M) could decrease the DMI-induced increase of DA (125±5%) and NE (130±6%).
On the other hand, local application of DA (12 nM、20 nM and 40 nM) into the mPFC concentration-dependently increased extracellular NE (119±3%、135±6% and 160±6%) in the mPFC. The D1 receptor antagonist SCH 23390 (10nM), but not D2 receptor antagonist eticlopride (1nM), could block the increase of extracellular NE, which was induced by local infusion of 40 nM DA.
These results suggest that in the mPFC (1) when the extracellular NE concentration increased, the DA concentration would also increase, which may be due to the action of NE on a1 receptors (heteroreceptor regulation) and the competitive effect of DA with NE for reuptake sites on the NE terminals (heterotransporter regulation); (2) DA terminals can regulate extracellular NE and this is due to the action of DA on D1 receptors to enhance NE release (heteroreceptor regulation).

中文摘要………………………………………2
英文摘要………………………………………5
背景介紹………………………………………7
研究動機………………………………………17
實驗目的………………………………………18
實驗材料………………………………………19
實驗方法………………………………………24
結果……………………………………………32
討論……………………………………………41
結論……………………………………………48
參考文獻………………………………………49
圖表………………………………………… 54

Andersson J.L., Marcus M., Nomikos G.G., Svensson T.H. (1994) Prazosin modulates the changes in firing pattern and transmitter release induced by raclopride in the mesolimbic, but not in the nigrostriatal dopaminergic system.. N-S. Arch Pharmacol. 349, 236-243.
Bayer V.E. and Pickel V.M. (1990) Ultrastructural localization of tyrosine hydroxylase in the rat ventral tegmental area: Relationship between immunolabeling density and neuronal associations. J.Neurosci. 10, 2996-3013.
Berger B., Tassin J.P., Blanc G., Moyne M.A., and Thierry A.M. (1974) Histochemical confirmation for dopaminergic innervation of the rat cerebral cortex after destruction of the noradrenergic ascending pathways. Brain Res. 81, 332-337.
Blanc G., Trovero F., Vezina P., Herve D., Godeheu A.M., Glowinski J., and Tassin J.P. (1994) Blockade of prefronto-cortical a1-adrenergic receptors prevents locomotorhyperactivity induced by subcortical D-amphtamine injection. Eur.J.Neurosci. 6,293-298.
Burgen A.S.V. and Iversen L.L. (1965) The inhibition of noradrenaline uptake by sympathomimetic amines in the rat isolated heart. Br. J. Pharmacol. Chemotherap. 25, 34.
Carboni E., Tanda L., Frau R, and Di Chiara G. (1990) Blockade of the noradrenaline carrier increase extracellular dopamine concentrations in the prefrontal cortex: evidence that dopamine is taken up in vivo by noradrenergic terminals. J. neurochem. 55, 1067-1070.
Dennis T., L`Heureux R., Carter C., and Scatton B. ( 1987 ) Presynaptic alpha-2 adrenoceptors play a major role in the effects of idazoxan on cortical noradrenaline release ( as measured by in vivo dialysis ) in the rat. J. Pharmacol. Exp. Ther. 241, 642-649.
Diamond I.T. (1979) The subdivisions of neocortex: A proposal to revise the traditional view of sensory, motor, and association areas, in Progress in Psychobiology and Physiological Psychology, Vol. 8 (Sprague J.M., and Epstein A.N., eds), pp. 1-43. Academic Press, New York.
Dubocovich M. L. (1984) Presynaptic receptors in the visual system. Ann. NY Acad. Sci. 430, 82-95.
Funk D. and Stewart J. (1996) Role of catecholamines in the frontal cortex in the modulation of basal and stress-induced autonomic output in rats. Brain Res. 741, 220-229.
Fuster Joaquin M. (1997) Neurophysiology, in The prefrontal cortex, pp. 146-149. Lippincott-Raven Publishers, New York.
Fuxe K., Agnati L.F., Kalia M., Goldstein M., Andersson K., and Harfstrand A. (1985) Dopaminergic systems in the brain and pituitary, in The Dopaminergic System in Basic and Clinical Aspects of Neuroscience (Fluckiger E., Muller E.E. and Thorner M.O., eds), pp11-18. Berlin: Springer-Verlag.
Gobert A., Rivet J.-M., Audinot V., Newman-tancredi A., Cistarelli L. and Millan M.J. (1998) Simultaneous quantification of serotonin, dopamine and noradrenaline levels in single frontal cortex dialysates of freely- moving rats reveals a complex pattern of reciprocal auto- and heteroreceptor-mediated control of release. Neuroscience 84, 413-429.
Grenhoff J., Johnson S.W., and North R.A. (1993) Alpha-adrenergic depolarization of rat midbrain DA neurons. Soc. Neurosci. Abstr. 19, 1374.
Grenhoff J., Nisell M., Ferre S., Aston-Jones G., and Svensson T.H. (1993) Noradrenergic modulation of midbrain dopamine cell firing elicited by stimulation of the locus coeruleus in the rat. J.Neural Transm. 93, 11-25.
Grenhoff J., Noth R.A., Johnson S.W. (1995) Alpha 1-adrenergic effects on dopamine neurons recorded intracellularly in the rat midbrain slice. Eur. J. Neurosci. 7, 1707-1713.
Grenhoff J.,and Svensson T.H. (1993) Prazosin modulates the firing pattern of dopamine neurons in the rat ventral tegmental area. Eur. J. Pharmacol. 233, 79-84.
Gresh P.J., Sved A.F., Zigmond M.J. and Finlay J.M. (1995) Local influence of endogenous morepinephrine on extracellular dopamine in rat medial prefrontal cortex. J. N eurochem. 65, 111-116.
Hertel P., Nomikos G., Iurlo M.and Svensson T.H. (1996) Risperidone:regional effects in vivo on release and metabolism of dopamine and serotonin in the rat brain. Psychopharmacology. 124, 74-86.
Horn A.S. (1973) Structure-activity relations for the inhibition of catecholamine uptake into synaptosomes from noradrenergic and dopaminergic neurones in rat brain homogenates. Br. J. Pharmacol. 47, 332.
Jones E.G., and Powell T.P.S. (1970) An experimental study of converging sensory pathways within the cerebral cortex of the monkey. Brain 93, 793-820.
Koob G.F. (1992) Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol. Sci. 13, 177-184.
Lindvall O., Bjorklund A., Moore R.Y., and Stenevi U. (1974) Mesencephalic dopamine neurons projecting to neocortex. Brain Res. 81, 325-331.
Mateo Y., Pineda J. and Meana JJ. (1998) Somatodendritic alpha2-adrenoceptors in the locus coeruleus are involved in the in vivo modulation of cortical noradrenaline release by the antidepressant desipramine. J.Neurochem. 71, 790-798.
Marien M. and Colpaert F. (1998) Inhibitory effects of a2-adrenoceptor agonists on cortical noradrenaline and striatal dopamine release in the mouse brain in vivo. Pierre Fabre Research Center, 17 avenue Jean Moulin, Castres 81106, France.
Meana JJ., Herrera M., Goiny M. and Silverira R. (1997) Modulation of catecholamine release by alpha2-adrenoceptors and I1-imidazoline receptors in rat brain. Brain Res. 744, 216-226.
Mesulam M.M., Van Hoesen G., Pandya D.N., and Geschwind N. (1977) Limbic and seneory connections of inferior parietal lobule (area PG) in the rhesus monkey: a study with a new method for horseradish peroxidase histochemistry. Brain Res. 136, 393-414.
Moghaddam B. and Bunney B.S. (1990) Acute effects of typical and atypical antipsychotic drugs on the release of dopamine from prefrontal cortex, nucleus accumbens, and striatum of the rat: an in vivo microdialysis study. J.Neurochem. 54, 1755-1760.
Nomikos G.G., Iurlo M., Andersson J.L., Kimura K. and Svensson T.H. (1994) Systemic administration of amperozide, a new atypical antipsychotic drug, preferentially increases dopamine release in the rat medial prefrontal cortex. Psychopharmacology. 115, 147-156.
Ohmori T., Koyama T. and Yamashita I. (1991) Measurement of endogenous dopamine and norepinephrine release from superfused slices of rat prefrontal cortex in vitro: modulation by D2 and alpha-2 presynaptic receptors. Life Sci. 48, 283-289.
Palkovits M. (1979) Dopaminelevels of individual brain regions: Biochemical aspects of DA distribution in the central nervous system, in The neurobiology of Dopamine (Horn A. S., Korf J., and Westerink B. H. C., eds), pp. 343-356. Academic Press, London.
Pozzi L., Invernizzi R., Cervo L., Vallebuona F. and Samanin R. (1994) Evidence that extracellular concentration of dopamine are regulated by noradrenergic neurons in the frontal cortex of rats. J. Neurochem 63, 195-200.
Raiteri M., Del Carmine R., Bertollini A., and Levi G.(1977) Effect of sympathomimetic amines on the synaptosomal transpot of noradrenaline, dopamine, and 5-hydroxytryptamine. Eur. J. Pharmacol. 41, 133-143.
Rossetti Z. L., Pani L., Portas C. and Gessa G. (1989) Brain dialysis provides evidence for D2-dopamine receptors modulating noradrenaline release in the rat frontal cortex. Eur. J. Pharmac. 163, 393-395.
Sallinen J., Link R. E., Haapalinna A., Viitamaa T., Kulatunga M., Sjoholm B., Macdonald E., Pelto-Huikko M., Leino T., Barsh G. S., kobilka B. K. and Scheinin M. (1997) Genetic alteration of a2C-adrenoceptor expression in mice: influence on locomotor, hypothermic, and neurochemical effects of dexmedetomidine, a subtype-nonselective a2-adrenoceptor agonist. Molec. Pharmac 51, 36-46.
Sesack S., Hawrylak V., Matus C., Guido M. and Levey A. (1998) Dopamine axon varicosities in the prelimbic division of the rat prefrontal cortex exhibit sparse immunoreactivity for the dopamine transporter. J. neurosci. 18, 2697-2708.
Slopsema J.S., van der Gugten J. and de Bruin. J.P. (1982) Regional concentrations of noradrenaline and dopamine in the frontal cortex of the rat: dopaminergic innervation of the prefrontal subareas and lateralization of prefrontal dopamine. Brain Res. 250, 197-200.
Sommermeyer H., Frielingsdorf J. and Knorr A. (1995) Effects of prazosin on the dopaminergic neurotransmission in rat brain. Eur. J. Pharmac. 276, 267-270.
Swanson L.W. (1981) The projections of the ventral tegmental area and study in the rat. Brain Res. Bull. 9, 321-354.
Tanda G., Pontieri F. E., Frau R..,and Di Chiara G. (1997) Contribution of blockade of the noradrenaline carrier to the increase of extracellular dopamine in the rat prefrontal cortex by amphetamine and cocaine. Eur. J. Neurosci. 10, 2007-2085.
Thierry A.M., Blanc G., Sobel A., Stinus L., and Glowinski J. (1973) Dopaminergic terminals in the rat cortex. Science 182, 499-501.
Trendelenburg A.U., Starke K., Limberger N. (1994) Presynaptic alpha 2A-adrenoceptors inhibit the release of endogenous dopamine in rabbit caudate nucleus slices. N-S Arch Pharmacol. 350, 473-481.
Ueda H., Goshima Y., and Misu Y. (1983) Presynaptic mediation by a2-, b1-, and b2-adrenoreceptors of endogenous noradrenaline and dopamine release from slices of rat hypothalamus. Life Sci. 33, 371-376.
Vahabzadeh A., Fillenz M. (1992) Studies on the origin of rat hippocampal dihydroxyphenylacetic acid using microdialysis. Neurosci Lett. 136, 51-55.
Vezina P., Blanc Gg., Glowinski J., and Tassin J. P. ( 1992 ) Opposed behavioural outputs of increased dopamine transmission in prefrontocortical and subcortical areas ; A role for the cortical D1 dopamine receptor. Eur. J. Neurosci. 3, 1001-1007.
Volonte M., Monferini E., Cerutti M., Fodritto F. and Borsini F. (1997) BMG80, a novel potential antipsychotic drug: evidence for multireceptor actions and preferential release of dopamine in prefrontal cortex. J.Neurochem. 69, 182-190.
Yamamoto B.K. and Novotney S. (1998) Regulation of extracellular dopamine by the norepinephrine transporter. J.Neurochem. 71, 274-280.

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