• The Korean Journal of Physiology and Pharmacology
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• v.11 no.4
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• pp.139-144
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• 2007

Recent studies suggest that alterations in glutamate receptor subunit levels in mesocorticolimbic dopamine areas could account for neural adaptations in response to psychostimulant drugs. Although many drugs of abuse induce changes in ionotropic glutamate receptor subunits in mesocorticolimbic dopamine areas, the changes of ionotropic glutamate receptor subunits by repeated nicotine treatment in these areas are not known. To answer this question, we injected male Sprague-Dawley rats twice daily with nicotine (0.4 mg/kg) or saline (1 ml/kg) for 10 days. The immunoreactivity of NR1, GluR1, and GluR2 glutamate receptor subunits was examined $16{\sim}18 h$ after the last injection of saline or nicotine. Repeated nicotine treatment significantly increased NR1 levels in the ventral tegmental area (VTA). In addition, repeated nicotine treatment showed a tendency towards an increase in GluR1 levels in the VTA as well as in striatum. However, there was no significant change in glutamate receptor subunits in other areas including nucleus accumbens (NAc). These results demonstrate that repeated nicotine treatment increases NR1 levels in VTA similarly to other drugs of abuse, suggesting that elevated glutamate receptor subunits in the VTA, but not NAc may be involved in the excitation of mesocorticolimbic dopamine neurons by nicotine.

• Molecules and Cells
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• v.45 no.9
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• pp.640-648
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• 2022

CD133, also known as prominin-1, was first identified as a biomarker of mammalian cancer and neural stem cells. Previous studies have shown that the prominin-like (promL) gene, an orthologue of mammalian CD133 in Drosophila, plays a role in glucose and lipid metabolism, body growth, and longevity. Because locomotion is required for food sourcing and ultimately the regulation of metabolism, we examined the function of promL in Drosophila locomotion. Both promL mutants and pan-neuronal promL inhibition flies displayed reduced spontaneous locomotor activity. As dopamine is known to modulate locomotion, we also examined the effects of promL inhibition on the dopamine concentration and mRNA expression levels of tyrosine hydroxylase (TH) and DOPA decarboxylase (Ddc), the enzymes responsible for dopamine biosynthesis, in the heads of flies. Compared with those in control flies, the levels of dopamine and the mRNAs encoding TH and Ddc were lower in promL mutant and pan-neuronal promL inhibition flies. In addition, an immunostaining analysis revealed that, compared with control flies, promL mutant and pan-neuronal promL inhibition flies had lower levels of the TH protein in protocerebral anterior medial (PAM) neurons, a subset of dopaminergic neurons. Inhibition of promL in these PAM neurons reduced the locomotor activity of the flies. Overall, these findings indicate that promL expressed in PAM dopaminergic neurons regulates locomotion by controlling dopamine synthesis in Drosophila.

• Korean Journal of Veterinary Research
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• v.32 no.2
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• pp.165-173
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• 1992

The present study was carried out to investigate the effects of dopaminergic drugs and the role of specific dopamine(DA) receptors on the release of TSH, $T_4$ and $T_3$. Serum TSH levels (cold-induced, $4{^{\circ}C}$) were determined using RIA(radioimmunoassay) at 30 min after administration of dopamine agonists and antagonists. Serum $T_4$ and $T_3$ levels were detected after these dopaminergic drugs were administered subcutaneously twice a day for a week. The results of the study are summarized as follows : Apomorphine, a nonspecific DA receptor agonist, produced a dose-depedent decrease in serum TSH, $T_4$ and $T_3$ levels. However, only low doses (0.3, 1.0mg/kg) of SKF38393, a specific $D_1$-receptor agonist, produced a decrease in serum lelvels of TSH. I,Y171555, a specific $D_2$-receptor agonist, produced a dose dependent decrease in serum TSH, $T_4$ and $T_3$ levels. However, SCH23390, a specific $D_1$-receptor antagonist, produced a decrease except in serum T levels which were increased dose dependently. High doses (1.0, 3.0mg/kg) of sulpiride, a specific $D_2$-receptor antagonist, made a increase in the serum levels of TSH and $T_3$. The effects of dopaminergic drugs in serum TSH and $T_4$ levels was potentiated by the pretreatment of apomorphine. The overall results of this study suggest that the regulation of TSH, $T_4$ and $T_3$ secretion were mediated via specific $D_1$ and $D_2$ receptor.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.1
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• pp.89-97
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• 2013

Developing an animal model for a specific disease is very important in the understanding of the underlying mechanism of the disease and allows testing of newly developed new drugs before human application. However, which of the plethora of experimental animal species to use in model development can be perplexing. Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a very well known method to induce the symptoms of Parkinson's disease in mice. But, there is very limited information about the different sensitivities to MPTP among mouse strains. Here, we tested three different mouse strains (C57BL/6, Balb-C, and ICR) as a Parkinsonian model by repeated MPTP injections. In addition to behavioral analysis, endogenous levels of dopamine and tetrahydrobiopterin in mice brain regions, such as striatum, substantia nigra, and hippocampus were directly quantified by liquid chromatography-tandem mass spectrometry. Repeated administrations of MPTP significantly affected the moving distances and rearing frequencies in all three mouse strains. The endogenous dopamine concentrations and expression levels of tyrosine hydroxylase were significantly decreased after the repeated injections, but tetrahydrobiopterin did not change in analyzed brain regions. However, susceptibilities of the mice to MPTP were differed based on the degree of behavioral change, dopamine concentration in brain regions, and expression levels of tyrosine hydroxylase, with C57BL/6 and Balb-C mice being more sensitive to the dopaminergic neuronal toxicity of MPTP than ICR mice.

• Bulletin of the Korean Chemical Society
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• v.21 no.10
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• pp.1035-1038
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• 2000

Vibrational properties of dopamine neutral species in powder state have been studied by means of the normal mode analysis based on the force constants obtained from the density functional calculation at B3LYP level and the results of Fourier trans form Raman and infrared spectroscopic measurements. Ab initio calculation at MP2 level shows that the trans conformer of dopamine has higher electronic energy about 1.4 kcal/mol than those of the gauche+ and the gauche-conformers, and two gauche conformers have almost the same energies. Free energies calculated at HF and B3LYP levels show very similar values for three conformers within 0.3 kcal/mol. Empirical force field has been constructed from force constants of three conformers, and refined upon ex-perimental Raman spectrum of dopamine to rigorous values. The major species of dopamine neutral base in the powder state is considered a trans conformer as shown in the crystallographic study of dopamine cationic salt.

• Journal of Acupuncture Research
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• v.20 no.4
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• pp.24-41
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• 2003

Objective: Dopamine activity in thenucleus accumbens is an important neuropharmacological component of morphine reinforcement. In this nucleus a shell and core have been distinguished on the basis of anatomical and neurochemical criteria. Although acupuncture has been standard intervention in many detoxication programs worldwide, the central mechanism by which morphine acts to reinforce behavior remain elusive. The present in vivo microdialysis study was conducted, in freely moving rats, to detect the effects of acupuncture on extracellular dopamine release in the nucleus accumbens. Methods: Male Sprague-Dawley rats received acupuncture for 1 min after injection of morphine hydrochloride (5mg/kg, s.c.). The employed acupuncture needle points corresponded to bilateral Neiguan(PC6) on the pericardium channel, which has been used to treat mental and psychosomatic disorders. Extracellular dopamine and its metabolites were measured every 20 mins for 3 hrs following the subcutaneous morphine injection. Results: Results showed that acupuncture at PC6 significantly attenuated increases in dopamine levels induced by a single acute morphine injection in the nucleus accumbens shell and core, respectively. Conclusions: These results provided strong evidence for acupuncture-mediated reduction in morphine-induced dopamine release in the rat nucleus accumbens.

• Biomolecules & Therapeutics
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• v.32 no.5
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• pp.568-576
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• 2024

Colorectal cancer (CRC) continues to demonstrate high incidence and mortality rates, emphasizing that implementing strategic measures for prevention and treatment is crucial. Recently, the dopamine receptor D2 (DRD2), a G protein-coupled receptor, has been reported to play multiple roles in growth of tumor cells. This study investigated the anticancer potential of domperidone, a dopamine receptor D2 antagonist, in HCT116 human CRC cells. Domperidone demonstrated concentration- and time-dependent reductions in cell viability, thereby inducing apoptosis. The molecular mechanism revealed that domperidone modulated the mitochondrial pathway, decreasing mitochondrial Bcl-2 levels, elevating cytosolic cytochrome C expression, and triggering caspase-3, -7, and -9 cleavage. Domperidone decreased in formation of β-arrestin2/MEK complex, which contributing to inhibition of ERK activation. Additionally, treatment with domperidone diminished JAK2 and STAT3 activation. Treatment of U0126, the MEK inhibitor, resulted in reduced phosphorylation of MEK, ERK, and STAT3 without alteration of JAK2 activation, indicating that domperidone targeted both MEK-ERK-STAT3 and JAK2-STAT3 signaling pathways. Immunoblot analysis revealed that domperidone also downregulated DRD2 expression. Domperidone-induced reactive oxygen species (ROS) generation and N-acetylcysteine treatment mitigated ROS levels and restored cell viability. An in vivo xenograft study verified the significant antitumor effects of domperidone. These results emphasize the multifaceted anticancer effects of domperidone, highlighting its potential as a promising therapeutic agent for human CRC.

• 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.

• Annals of Clinical Neurophysiology
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• v.10 no.2
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• pp.98-100
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• 2008

Restless legs syndrome (RLS) is a sensorimotor neurological disorder in which the primary symptom is a compelling urge to move the legs, accompanied by unpleasant and disturbing sensations in the legs. Although pathophysiologic mechanism of RLS is still unclear, several evidences suggest that RLS is related to dysfunction in central nervous system involving brain and spinal cord. L-DOPA, as the precursor of dopamine, as well as dopamine agonists, plays an essential role in the treatment of RLS leading to the assumption of a key role of dopamine function in the pathophysiology of RLS. Patients with RLS have lower levels of dopamine in the substantia nigra and respond to iron administration. Iron, as a cofactor in dopamine production, plays a central role in the etiology of RLS. Functional neuroimaging studies using PET and SPECT support a central striatal D2 receptor abnormality in the pathophysiology of RLS. Functional MRI suggested a central generator of periodic limb movements during sleep (PLMs) in RLS. However, to date, we have no direct evidence of pathogenic mechanisms of RLS.

• 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.