• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.11-18
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• 1992

Rats were treated with physostigmine, using 0.75 mg/kg acutely, with 0.75 mg/kg daily for 7 dats, or with 0.15 mg/kg/h continuously for 7 days. Striatal dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels and tyrosine hydroxylase (TH) activities were studied. After acute treatment striatal DOPAC and HVA concentrations were significantly increased without changes in DA level 1 h, but not 24 h. And also the ratios of DOPAC/DA and HVA/DA were increased, suggesting an increased turnover of DA. however TH activities were decreased 24h, but not 1h after acute administration. After both daily and continuous treatment with physostigmine for 7 days, neither DA nor its metabolites were changed. However their ratios were decreased, suggesting a decreased turnover of DA. The TH activities were only decreased in the daily treated group, but not in the continously treated one. These results indicate that dopamine metabolisms are changed after acute and subacute administration with physostigmine. Further it suggest that the subacute stimulation of cholinergic activity may induce the dopamine metablism and activity to be decreased.

• Archives of Pharmacal Research
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• v.18 no.4
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• pp.249-255
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• 1995

The changes in the levels of the extracellular dopamine metabolites and the responses to various dopamine agents were studied by using microdialysis inhyperglycemic rat striatum. The hyperglycemia were induced by the administriation of streptozotocin (40 mg/kg, i.p. for 3 days.). The basal levels of striatal dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were significantly decreased in hyperglycemic rat striatum. After the administration ofl D-1 and D-2 receptor antagonists, SCH-23390 and (-)sulpiride, to rats 14 days after the last administration of STZ, the increased rates in DOPAC levels were higher in hyper- than in normoglycemic rats. However, after the administration of dopamine autoeceptor agonist, 3(-)PPP, the levels of the extracellular HVA were increased in normoglycemic rats, but those were not altered in hyperglycemic rats. The results indicate that the striatal dopamine activities were decreased in the hyperglycemic rats and suggest that release of dopamine may be decreased in hyperglycemic rats. Furthermore it suggest that the increase in the levels of the extracellular dopamine metabolites by dopamine antagonists might be dur to the incrrased sensitivities of the dopamine receptors in hyperglycemic state.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.1
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• pp.9-14
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• 2002

In the present study, we used the microdialysis technique combined with high performance liquid chromatography (HPLC) and electrochemical detection to measure the extracellular levels of norepinephrine (NE) in the posterior hypothalamus in vivo, and to examine the effects of various drugs, affecting central noradrenergic transmission, on the extracellular concentration of NE in the posterior hypothalamus. Microdialysis probes were implanted stereotaxically into the posterior hypothalamus (coordinates: posterior 4.3 mm, lateral 0.5 mm, ventral 8 mm, relative to bregma and the brain surface, respectively) of rats, and dialysate collection began 2 hr after the implantation. The baseline level of monoamines in the dialysates were determined to be: NE $0.17{\pm}0.01,$ 3,4-dihydroxyphenylacetic acid (DOPAC) $0.94{\pm}0.07,$ homovanillic acid (HVA) $0.57{\pm}0.05$ pmol/sample (n=8). When the posterior hypothalamus was perfused with 90 mM potassium, maximum 555% increase of NE output was observed. Concomitantly, this treatment significantly decreased the output of DOPAC and HVA by 35% and 28%, respectively. Local application of imipramine $(50\;{\mu}M)$ enhanced the level of NE in the posterior hypothalamus (maximum 200%) compared to preperfusion control values. But, DOPAC and HVA outputs remained unchanged. Pargyline, an irreversible monoamine oxidase inhibitor, i.p. administered at a dose of 75 mg/kg, increased NE output (maximum 165%), while decreased DOPAC and HVA outputs (maximum 13 and 12%, respectively). These results indicate that NE in dialysate from the rat posterior hypothalamus were neuronal origin, and that manipulations which profoundly affected the levels of extracellular neurotransmitter had also effects on metabolite levels.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.221-221
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• 1996

(중략) 1)에탄올 0.08g/kg 급성투여군은 선조체 5-HT, DOPAC, HVA, DOPAC/DA, HVA/DA ratio를 현저히 증가시켰다. 반면, 3g/kg 급성투여군은 도파민 및 세로토닌 신경활성에 전혀 영향을 미치지 않았다. 2) 에탄을 3g/kg을 21회 연속투여군은 선조체 DA 및 5-HT와 5-HIAA 함량을 유의성있게 증가하였으나 도파민 대사산물에는 영향을 주지 않았다. 3) 35주령 흰쥐는 에탄을 3g/kg 급성투여군에서 5-HT함량을 감소시켰으나 3g/kg 21회 연속투여군은 5-HT함량을 유의성있게 증가시켰다. 4) 7주령과 35주령 모두 21회 연속투여에서 DA 및 5-HT함량을 현저히 증가시켰다.

• Archives of Pharmacal Research
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• v.18 no.4
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• pp.271-276
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• 1995

Changes in the distribution of dopamine and its metabolites, activities of monoamine oxidase, and dopamine uptake were studied inhyperglycemic rat striatum. The hyperglycemia was induced by the administration of streptozotocin (STZ, 40 mg/kg, i.p. for 3 days.). The levels of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid were significantly decreased without change in dopamine level in the synatic cleft 14 days after STZ treatment. In the synaptosome, the dopamine level, however, was significanly increased after the treatment. But the DOPAC level in the synaptosome was decreased 14 days after the treatment. The affinity of dopamine uptake was significantly decreased without changes in the velocity 14 days after the treatment. However the response to uptqke inhibitor was unchanged. The striatal monoamine oxidase activities were also decreased in the hyperglycemic state. These results indicate that various parameters of striatal dopamine activities were decreased in the hyperglycemic rats. Furthermore, it suggests that the increase in dopamine level of synaptosome might be due to the decrease in the release of dopaine in hyperglycemic state.

• YAKHAK HOEJI
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• v.43 no.1
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• pp.33-41
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• 1999

Whereas as selective inhibitor of monoamine oxidase type B, ${\ell}-deprenyl$ (selegiline), is now widely used in the treatment of Parkinson's disease, the precise action mechanism of the drug remains elusive. In this study, to investigate protective effect of ${\ell}-deprenyl$ against the dopamine depletion induced by 6-hydroxydopamine (6-OHDA), the changes in tissue contents of dopamine, serotonine (5-HT) and their metabolites by ${\ell}-deprenyl$ were examined in intact and 6-OHDA-lesioned rat brain. In intact rats, a single intraperitoneal (i.p.) administration of ${\ell}-deprenyl$ showed a no change in striatal dopamine and its metabolites at low concentrations (0.25 and 1 mg/kg), but significantly inhibited dopamine metabolism at a higher concentration (10 mg/kg). The repeated administration of ${\ell}-deprenyl$ (0.25 and 1 mg/kg, i.p., for 21 consecutive days) reduced the contents of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) in dose-dependent manners without changes in dopamine content. Bilateral intracerebroventricular (i.c.v) infusion of 6-OHDA ($100{\;}\mu\textrm{g}/10{\;}{\mu}{\ell}/hemisphere$) depleted dopamine in striatum and septum by 81% and 90% respectively. When rats were pretreated with ${\ell}-deprenyl$ before 6-OHDA administration, the striatal and septal dopamine levels were significantly increased by about 3.0-fold and 3.4-fold, respectively, compared to the untreated 6-OHDA-lesioned rat. Pretreatment of ${\ell}-deprenyl$ also significantly enhanced the dopmaine metabolites, DOPAC, HVA and 3-methoxytyramine, in the striatum, and DOPAC in the septum. These results indicate that a ${\ell}-deprenyl$ pretreatment prevents 6-OHDA-induced depletion of striatal dopamine and its metabolites.

• Clinical and Experimental Pediatrics
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• v.46 no.8
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• pp.789-794
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• 2003

Purpose : We intended to evaluate the effect of hypoxia-ischemia on extracellular striatal monoamine metabolism in neonatal rat brains by in vivo microdialysis. Methods : The right common carotid arteries of five or six-day old rats were surgically ligated, and the probes for microdialysis were inserted into the right striatum with stereotaxic instrument. After stabilization for two hours, artificial cerebrospinal fluid was infused via the probe for microdialysis and samples were collected during hypoxia-ischemia and recovery periods at 20 minute intervals. The concentrations of DA(dopamine), DOPAC(3,4-di-hydroxyphenyl acetic acid), HVA(homovanillic acid), NE(norepinephrine), and 5-HIAA(5-hydroxy indole-acetic acid) were measured by HPLC(high performance liquid chromatography) and the changes were analysed. Results : The striatal levels of dopamine metabolites such as DOPAC and HVA, were significantly decreased during hypoxia-ischemia, and increased to their basal level during reoxygenation(P<0.05). Dopamine mostly increased during hypoxia but statistically not significant(P>0.05). DOPAC showed the most remarkable decrease($23.0{\pm}4.2%$, P<0.05), during hypoxia-ischemia and increase to the basal levels during reoxygenation($120.8{\pm}54.9%$, P<0.05), and HVA showed the same pattern of changes as those of DOPAC during hypoxia-ischemia($35.3{\pm}7.6%$ of basal level, P<0.05) and reoxygenation ($105.8{\pm}32.3%$). However, the level of NE did not show significant changes during hypoxia-ischemia and reoxygenation. The levels of 5-HIAA decreased($74.9{\pm}3.1%$) and increased($118.1{\pm}7.8%$) during hypoxia-ischemia and reoxygenation, respectively(P<0.005). Conclusion : Hypoxia-ischemia had a significant influence on the metabolism of striatal monoamine in neonatal rat brains. These findings suggest that monoamine, especially dopamine, and its metabolites could have a significant role in the pathogenesis of hypoxic-ischemic injury of neonatal rat brains.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.1-9
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• 1992

Catecholamines, serotonin and their metabolites were measured in the posterior hypothalamus of urethane-anesthetized normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) using brain microdialysis which is a recently developed experimental method to measure the release of neurotransmitters and their metabolites at the localized brain area in vivo. Microdialysis probe was implanted stereotaxically to the rat posterior hypothalamus and perfused by Ringer's solution. Monoamines and their metabolites were quantified by reverse phase high performance liquid chromatography with electrochemical detection. In vitro recovery test of microdialysis showed that there exist inverse relationship between the perfusion flow rate and the relative recovery of neurochemical compounds. The estimated extracellular concentration of dopamine was about 32 nM, of norepinephrine 50 nM, of epinephrine 50 nM, of serotonin 73 nM, of 3, 4-dihydroxyphenylacetic acid (DOPAC) 281 nM, of homovanillic acid (HVA) 181 nM, and of 5-hydroxyindoleacetic acid (5HIAA) 3767 nM in the hypothalamic perfusate of the normotensive rat. There was no difference in the basal level of monoamines between the SHR and the WKY. In contrast, the level of DOPAC, HVA and 5HIAA in SHR was higher than that in the WKY, This study demonstrated that the microdialysis technique should be an applicable tool for in vivo measurement of central neurochemical substances.

• Analytical Science and Technology
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• v.8 no.2
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• pp.215-220
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• 1995

A simple, efficient and sensitive method was described for the simultaneous determination of catecholamine, indoleamine and related metabolites from the homogenates of the rat brain striatum by HPLC-ECD. The optimum mobile phase on a reverse phase $C_{18}$ column was 35mM sodium acetate buffer(included 10mM citric acid, 0.13mM $Na_4EDTA$, 0.58mM SOS, pH3-4):MeOH=85:15. The column temperature was $30^{\circ}C$. Dopamine(DA), 3, 4-dihydroxyphenyl acetic acid(DOPAC), homovanilic acid(HVA), 5-hydroxyindole acetic acid(5-HIAA), serotonin(5-HT) and noradrenaline(NA) could be separated and analysed to very small amount. The detection limits of this method were 2~10pg per injection for all components. The effects of age and sex of rat on the contents of the catecholamines and their metabolites in rat brain striatum were studied. The levels of DA and 5-HT contents of the 7 week old female rats were higher than those of the 7 week old male rats. As the age of rat increases, the contents of DOPAC increased significantly.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1992.05a
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• pp.34-34
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• 1992

심혈관계의 중추 조절작용과 고혈압 치료제의 작용기전을 규명하기 위한 연구의 한 단계로서 생체내 미세투석법(in vivo microdialysis)을 이용하여 후 시상하부의 국소부위에서 catecholamine들과 serotonin 및 그 대사체들의 세포와 농도의 변화를 정상혈압 횐쥐 (WKY)에서 관찰하고, 자연발생성 고혈압 횐쥐(SHR)에서 이들의 기준치를 비교하였다. 뇌정위 고정장치에 의해서 미세투석관을 후 시상하부에 위치시킨 후 링거액으로 관류하였다. 모노아민들과 그 대사체들은 고속액체 크로마토그라피와 전기화학 검출기률 이용하여 정량하였다. WKY에서 imipramine(50$\mu$M)의 관류에 의하여 norepinephrine의 농도가 유의하게 증가되었고, 또한 Pargyline (75mg/kg, i.p.)에 의하여 norepinephrine의 농도는 유의하게 증가된 반면에 DOPAC, HVA 및 5-HIAA는 감소하였다. WKY와 SHR에서 비교하였을때 norepinephrine, epinephrine, dopamine, serotonin의 농도는 차이가 없었으나 DOPAC, HVA, 5-HIAA의 농도는 SHR에서 유의하게 증가된 결과를 얻었다. 상의 결과들은 모노아민중에서 norepinephrine이 정상혈압 흰쥐의 후 시상하부에서 유리되는 주된 신경전달물질임을 시사한다. 또한 자연 발생성 고혈압 흰쥐의 후 시상하부에서 dopamine과 serotonin의 교체속도가 증가되었을 가능성이 큰 것으로 사료된다.