• The Korean Journal of Physiology and Pharmacology
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• 제9권5호
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• pp.263-268
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• 2005

Striatum has important roles in motor control, habitual learning and memory. It receives glutamatergic inputs from neocortex and thalamus, and dopaminergic inputs from substantia nigra. We examined effects of dopamine (DA) on the corticostriatal synaptic transmission using in vitro extracellular recording technique in rat brain corticostriatal slices. Synaptic responses were elicited by stimulation of cortical glutamatergic inputs on the corpus callosum and recorded in the dorsal striatum. Corticostriatal population spike (PS) amplitudes were decreased ($39.4{\pm}7.9$%) by the application of $100{\mu}M$ DA. We applied receptor subtype specific agonists and antagonists and characterized the modulation of corticostriatal synaptic transmission by different DA receptor subtypes. $D_2$ receptor agonist (quinpirole), antagonist (sulpiride), and $D_1$ receptor antagonist (SKF 83566), but not $D_1$ receptor agonist (SKF 38393), induced significantly the reduction of striatal PS. Pretreatment neither with SKF 83566 nor sulpiride significantly affected corticostriatal synaptic inhibition by DA. However, the inhibition of DA was completely blocked by pretreatment with mixed solution of both SKF 83566 and sulpiride. These results suggest that DA inhibits corticostriatal synaptic transmission through both $D_1$ and $D_2$ receptors in concert with each other.

• The Korean Journal of Physiology and Pharmacology
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• 제13권3호
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• pp.147-151
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• 2009

Repeated psychostimulants induce electroencephalographic (EEG) changes, which reflect adaptation of the neural substrate related to dopaminergic pathways. To study the role of dopamine receptors in EEG changes, we examined the effect of apomorphine, the dopamine D1 receptor antagonist, SCH-23390, and the D2 receptor antagonist, haloperidol, on EEG in rats. For single and repeated apomorphine treatment groups, the rats received saline or apomorphine for 4 days followed by a 3-day withdrawal period and then apomorphine (2.5 mg/kg, i.p.) challenge after pretreatment with saline, SCH-23390, or haloperidol on the day of the experiment. EEGs from the frontal and parietal cortices were recorded. On the frontal cortex, apomorphine decreased the power of all the frequency bands in the single treatment group, and increased the theta (4.5 ${\sim}$ 8 Hz) and alpha (8 ${\sim}$ 13 Hz) powers in the repeated treatment group. Changes in both groups were reversed to the control values by SCH-23390. On the parietal cortex, single apomorphine treatment decreased the power of some frequency bands, which were reversed by haloperidol but not by SCH-23390. Repeated apomorphine treatment did not produce significant changes in the power profile. These results show that adaptation of dopamine pathways by repeated apomorphine treatment could be identified with EEG changes such as increases in theta and alpha power of the frontal cortex, and this adaptation may occur through changes in the D1 receptor and/or the D2 receptor.

• 생물정신의학
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• 제6권2호
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• pp.259-263
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• 1999

Nefazodone, a newer antidepressant is a phenylpiperazine derivative that inhibits the reuptake of both norepinephrine and serotonin, and antagonizes $5-HT_{2A}$ and ${\alpha}_1$ adrenergic receptors. Compared with SSRIs, nefazodone caused the fewer activating symptoms, adverse gastrointestinal effects(nausea, diarrhea, anorexia) and adverse effects of sexual function, but is associated with the more dizziness, dry mouth, constipation, visual disturbances and confusion. We report on 4 cases of visual disturbances and hallucinations in patients taking nefazodone. It is not certain what mechanisms mediated these side effects, but three mechanisms are possible. 1) Nefazodone, as a 5-HT2 antagonist, might induce visual disturbances. 2) mCPP, metabolite of nefazodone might contribute to the hallucination through action on 5-HT receptor. 3) Dopaminergic enhancing activity of nefazodone might cause hallucination. These case report raises the possibility that dose-related perceptual disturbances may exist with nefazodone. The fact emphasizes the need to pay close attention to all possible drug interactions, particularly in patients treated with multiple psychoactive agents, older patients, and patients with decreased hepatic function.

• Biomolecules & Therapeutics
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• 제2권4호
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• pp.316-321
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• 1994

This study was undertaken to estimate whether nalbuphine, a mixed agonist/antagonist opioid analgesic produced psychic dependence. Moreover, the physical dependence liability of nalbuphine was compared with that of morphine after 7 days administrations of the drugs in mice and rats, and the effects of ginseng total saponin (GTS) on the development of physical dependence on nalbuphine were also studied. Nalbuphine did not produce psychic dependence. However, various abstinence signs precipitated by naloxone were observed in nalbuphine-dependent mice and rats. As the nature of the dependence syndrome produced by nalbuphine 30 mg/kg under these conditions seems similar to that induced by morphine 10 mg/kg, it is clear that nalbuphine possesses the substantial abuse potential. Therefore, nalbuphine may be needed to initiate more stringent controls for the prevention of nalbuphine abuse. On the other hand, GTS inhibited the development of physical dependence on nalbuphine and reduced the contents of dopamine and its metabolite in the brains of mice. Accordingly, results of this study suggest that the inhibitory effects of GTS on the development of physical dependence on nalbuphine may involve dopaminergic mechanism. GTS may be useful for the therapy of physical dependence on nalbuphine.

• 대한약리학회지
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• 제30권1호
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• pp.87-100
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• 1994

도파민 함유세포가 교감신경절에 존재하는 것으로 알려져 있으나, 말초에서 신경전달 물질로써 그의 역할과 작용기전에 대해서 아직까지 알려진 바가 많지 않다. 따라서 본 연구에서는 도파민 $D_2$-수용체의 선택적인 효능약으로 알려진 apomorphine이 흰쥐 적출 관류 부신에서 카테콜아민(CA)분비작용에 미치는 영향을 연구코자 시도하여 다음과 같은 연구결과를 얻었다. $10{\um}M\;Apomorphine$의 비교적 낮은 농도를 부신정맥내에 20분간 관류 하였을때 5.32mM ACh, 56mM KCl, $100{\mu}M$ DMPP 및 $100{\mu}M$ McN-A-343 등의 투여에 의한 CA 분비작용이 의의 있게 감소되었다. Apomorphine 농도를 $30{\mu}M$로 증가시켜 관류하였을때 상기약물에 의한 CA 분비작용은 더욱 억제되었으며 또한 Bay-K-8644에 의한 $100{\mu}M$의 고농도로 전처치 하였을때, ACh, excess $K^+$, DMPP 및 McN-A-343에 의한 CA분비작용은 현저히 차단되었다. 도파민 $D_2$-수용체 차단제인 metoclopramide $(30{\mu}M)$으로 20분간 관류 하였을때 ACh, DMPP 및 McN-A-343에 의한 CA 분비작용은 유의하게 억제된 효과를 나타내었으나 $excess\;{K^+}$에 의한 CA분비작용은 별다른 영향을 받지 않았다. 그러나 metoclopramide $(30{\mu}M)$ 존재하에서 $30{\mu}M$ apomorphine으로 20분간 전처치 하였을때 $excess{K^+}$ 뿐만 아니라 DMPP의 CA 분비작용은 별다른 변화를 받지 않았다. 이상과 같은 실험 연구결과를 종합하여 보면, apomorphine은 cholinergic receptor stimulation과 membrane depolarization에 의한 CA 분비작용을 용량의존적으로 억제하여, 이러한 작용은 억제성 도파민 수용체를 활성화 시킴으로써 흰쥐 부신 수질의 chromaffin cell 내로 칼슘의 유입을 억제하여 나타나는 것으로 사료된다.

• 생물정신의학
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• 제3권2호
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• pp.262-268
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• 1996

It has been known that clozapine is more selective mesolimbic dopamin $D_2$ receptor antagonist and related to 5-HT receptor. In this study, we wxamined the plasma homovanillic acid(HVA), serotonin(5-HT), and 5-hydroxyindoleacetic acid(5-HIM) levels in refractory schizophrenics during clozapine treatment. And we assessed the effects of clozapine on these plasma monoamine metabolites and their association with psychopathology and treatment response. Eight refractory schizophrenic patients(DSM-IV) have entered the study for 3 months during clozapine treatment. Patients were admitted to the inpatient sevice and withdrawn from all neuroleptics for 7-14 days but exceptionally occasional doses of lorazepam was given if needed for behavioral control. The dose of clozapine was titrated as tolerated to 800mg/day. The plasma HVA. 5-HIM and 5-HT levels were measured before treatment and following 2nd week, 4th week, 8th week, and 12th during treatment. Psychopathology was assessed with Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Synrome Scale(PANSS) before and during clozapine treatment. During clozapine treatment, no statistically significant changes were found in plasma HVA, 5-HIM, 5-HT levels, and HVA/5-HIM ratio between baseline and following 2nd week, 4th week, 8th week, 12th week. However, the change in plasma 5-HIAA/5-HT ratio from baseline to 4th week was statistically significant. Generally, changes of plasma HVA, 5-HIAA, 5-HT levels and HVA/5-HIAA ratio were not associated with psychopathology but 5-HIAA was associated with in positive symptoms and general psychopathology of PANSS. These results suggest that clozapine has been found to have relatively weak dopaminergic blokade and stronger serotonergic antagonism.

• The Korean Journal of Pain
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• 제14권1호
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• pp.46-50
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• 2001

Background: Ondansetron is both a central and peripheral serotonin (5HT) receptor antagonist and droperidol is a dopaminergic blocking drug which acts centrally at the chemoreceptor trigger zone. We assessed the efficacy and adverse effects of ondansetron, droperidol or both, in the prevention of postoperative emesis during postoperative intravenous patient-controlled analgesia (PCA) using butorphanol and ketorolac medication. Methods: We studied 60 women, aged 25-60 yrs, who underwent total abdominal hysterectomy (TAH), under general anesthesia using $N_2O-O_2$-enflurane. A bolus dose of 1 mg of butorphanol and 4 mg of ondansetron were given to patients and thereafter, PCA was started using 10 mg of butorphanol and 240 mg of ketorolac mixed into the 5% D/W solution (total volume; 100 ml, 1 ml of bolus dose, and 10 min of lockout interval). We also added ondansetron 4 mg (Group O, n = 20), ondansetron 4 mg and droperidol 2.5 mg (Group OD, n = 20), or droperidol 2.5 mg (Group D, n = 20) to the PCA drug. The severity of pain, nausea, vomiting, sedation and other side effects were assessed at 0, 1, 2, 6, 12, 24, 36 and 48 hr after awakening. Results: There was no difference in the incidence of nausea and vomiting between the three group [Group O: 4 (20%) and 3 (15%), respectively; Group OD: 1 (5%) and 1 (5%), respectively; Group D: 3 (15%) and 3 (15%), respectively]. Group O showed a lower sedation score than the other groups (P < 0.05). The pain score and other side effects did not show any difference between the groups. Conclusions: The combination of ondansetron and droperidol showed no clinical benefit compared with ondansetron or droperidol alone for prevention of postoperative nausea and vomiting during postoperative PCA using butorphanol and ketorolac.

• Biomolecules & Therapeutics
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• 제17권1호
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• pp.32-42
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• 2009

The purpose of the present study was to examine the effect of dihydrexidine, a full $D_1$ receptor agonist, on the secretion of catecholamines (CA) from the perfused model of the rat adrenal gland, and to establish its mechanism of action. Dihydrexidine (10-100 ${\mu}M$), perfused into an adrenal vein for 60 min, relatively produced dose- and time-dependent inhibition in the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM), DMPP (100 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Dihydrexidine itself did fail to affect basal CA output. Also, in adrenal glands loaded with dihydrexidine (30 ${\mu}M$), the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}M$), an activator of L-type $Ca^{2+}$ channels, cyclopiazonic acid (10 ${\mu}M$), an inhibitor of cytoplasmic $Ca^{2+}$-ATPase, and veratridine, an activator of voltage-dependent $Na+$ channels (10 ${\mu}M$), were also markedly inhibited, respectively. However, in the simultaneous presence of dihydrexidine (30 ${\mu}M$) and R (+)-SCH23390 (a selective antagonist of $D_1$ receptor, 3 ${\mu}M$), the CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644, cyclopiazonic acid and veratridine were considerably recovered to the extent of the corresponding control secretion compared with the inhibitory responses by dihydrexidinetreatment alone. In conclusion, these experimental results suggest that dihydrexidine significantly inhibits the CA secretion evoked by cholinergic stimulation (both nicotinic and muscarinic receptors) and membrane depolarization from the rat adrenal medulla. It seems that this inhibitory effect of dihydrexidine may be mediated by inhibiting influx of both $Ca^{2+}$ and $Na^+$ into the cytoplasm as well as by suppression of $Ca^{2+}$ release from cytoplasmic calcium store through activation of dopaminergic $D_1$ receptors located on the rat adrenomedullary chromaffin cells.

• 대한핵의학회지
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• 제35권4호
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• pp.258-267
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• 2001

Purpose/Methods: Repeated administration of methamphetamine (METH) produces high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. The effect of MK-801, a noncompetitive N-methyl-D-aspartate receptor antagonist, on METH-induced changes in DA transporter (DAT) and DA release evoked by an acute METH challenge was evaluated in rodent striatum uslng $[^3H]$]WIN 38,428 ex vivo auto-radiography and in vivo microdialysis. Results: Four injections of METH (10 mg/kg, i.p.), each given 2 h apart, produced 71% decrease in DAT levels in mouse striatum 3 d after administration. Pretreatment with MK-801 (2.5 mg/kg, i.p.) 15 min before each of the four METH injections protected completely against striatal DAT depletions. Four injections of MK-801 alone did not significantly change striatal DAT levels. Striatal DA release evoked by an acute METH challenge (4 mg/kg, i.p.) at 3 d after repeated administration of METH in rats was decreased but significant compared with controls, which was attenuated by repeated pretreatment with MK-801. Also, repeated injections of MK-801 alone attenuated acute METH-induced striatal DA release 3 d after administration. Conclusion: These results suggest that repeated administration of MK-801 may exert a preventive effect against METH-induced DA terminal injury through long-term attenuation of DA release induced by METH and other stimuli.

• 대한약리학회지
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• 제21권1호
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• pp.49-61
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• 1985

가토 측뇌실내로 dopamine을 투여하면 항이뇨를 일으키고, 도파민 길항제 haloperidol은 소량에서는 항이뇨를, 대량에서는 이뇨와 Na 배설증가를 초래한다는 보고에 비추어, 본 연구에서는 중추를 통한 신장기능 조절에 관여하는 도파민 수용체의 역할을 구명코자, D-2 receptor agonist이고 D-1 antagonist인 bromocriptine(BRC)의 작용을 검토하였다. 측뇌실내로 BRC를 투여하면 20-600 ${\mu}g/kg$의 범위안에서 대략 용량에 비례하여 natriuresis와 이뇨가 나타났으나, 신혈류와 사구체 여과율은 증량에 따라 점차 감소하였다. 따라서 이뇨 및 Na 배설증가는 신세뇨관에서의 Na재흡수 감소에 의한 것임을 알수 있었다. 이러한 Na 배설증가는 $200{\mu}g/kg$에서 가장 현저하여 Na 배설분획은 약 10%에 달하였다. 그러나 $600{\mu}g/kg$ 에서는 일시적인 현저한 혈압상승에 따르는 급격한 감소로 인하여 일시적 폐뇨가 선행한 다음 이뇨 작용이 나타났다. BRC의 정맥내 투여시에는 전신혈압 하강에 따르는 신혈류역학의 감소와 아울러 항이뇨가 나타났으며, 이는 측피실내로 투여한 BRC의 작용은 전신순환내로 유입되어 초래될 수도 있는 직접신장작용에 기인한것이 아니고 중추를 통한 것임을 시사하였다. Dopamine 150 ${\mu}g/kg$을 측뇌실내로 투여한 후에도 BRC 200 ${\mu}g/kg$은 작용을 나타낼 수 있으나, dopamine 500 ${\mu}g/kg$에 의해서는 BRC의 작용이 소실 되었다. 24 시간전에 1 mg/kg의 reserpine으로 처리한 가토에서는 200 ${\mu}g/kg$ BRC의 작용이 오히려 더 빠르고 강화되었다. 일측신장 신경을 제거한 표본에서는, BRC투여로 대조신은 항이뇨를 나타냈으나 실험신(탈신경측)은 심한 이뇨와 Na배설 증가를 일으켰다. 이상의 실험결과는, 측뇌실내 BRC는 natriuretic factor를 유리시킴과 동시에 교감신경 긴장도를 증가시키는 것을 시사하였으며, 또한 가토 신장기능의 중추 도파민계를 통한 조절에 있어서 여러 도파민 수용체가 각각 다른 기능을 하고 있음을 시사하였다.