• Biomolecules & Therapeutics
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• 제6권1호
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• pp.25-30
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• 1998

The roles of dopamine(DA) and N-methyl-D-aspartate(NMDA) system in the development and expression of morphine dependence were investigated by monitoring the concentrations of extracellular DA and its metabolites by in vivo microdialysis and simultaneous observation of behavioral changes in morphine dependent rats. Extracellular DA level in caudate putamen of morphine-dependent rat was decreased and the concentrations of its metabolites, dihydroxy phenylacetic acid(DOPAC) and homovanillic acid(HVA), were increased during naloxone-precipitated withdrawal. DA contents were recovered to normal levels by pretreatment of MK-801, a noncompetitive NMDA receptor antagonist, which may explain the mechanism of diminishing effect of MK-801 on withdrawal symptoms in morphine-dependent rats. MK-801(0.3 mg/tg, i.p.) induced the untoward hamful neurological signs such as ataxia and severe rotations, which may be produced by hyperactivation of dopaminergic system. These results suggest that MK-801 may inhibit the expression of mophine dependence by altering the dopamine release.

• Biomolecules & Therapeutics
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• 제21권6호
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• pp.476-480
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• 2013

Obesity is one of the most serious health problems in developed countries. It negatively affects diverse aspects of human wellbeing. Of these, a relationship between obesity and depression is widely recognized but biomarkers for assessment of obesity-associated mood changes in animal obesity models are rarely known. Here we explored the link between obesity and the plasma levels of monoamine neurotransmitters involved in mood control using a sensitive UPLC/MSMS technique in high fat diet (HFD)-induced obesity model in male C57BL/6 mice to explore the potential utility of plasma tests for obesity-associated mood change. HFD (60% of total calories, 8 weeks) induced significantly higher weight gains in body (+37.8%) and fat tissue (+306%) in male C57BL/6 mice. Bioanalysis of serotonin, dopamine and norepinephrine in plasma at 8 weeks of HFD revealed that serotonin decreased significantly in the obese mice when compared to normal diet-fed mice ($2.7{\pm}0.6$ vs $4.3{\pm}2.0ng/ml$, N=8). Notably, a negative correlation was found between the levels of serotonin and body weight gains. Furthermore, principal component analysis (PCA) with the individual levels of neurotransmitters revealed that plasma levels of dopamine and serotonin could apparently differentiate the obese mice from lean ones. Our study demonstrated that blood plasma levels of neurotransmitters can be employed to evaluate the mood changes associated with obesity and more importantly, provided an important clue for understanding of the relationship between obesity and mood disorders.

• Biomolecules & Therapeutics
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• 제31권4호
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• pp.411-416
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• 2023

Methamphetamine (METH) is a powerful neurotoxic psychostimulant affecting dopamine transporter (DAT) activity and leading to continuous excess extracellular dopamine levels. Despite recent advances in the knowledge on neurobiological mechanisms underlying METH abuse, there are few effective pharmacotherapies to prevent METH abuse leading to brain damage and neuropsychiatric deficits. α-Pinene (APN) is one of the major monoterpenes derived from pine essential oils and has diverse biological properties including anti-nociceptive, anti-anxiolytic, antioxidant, and anti-inflammatory actions. In the present study, we investigated the therapeutic potential of APN in a METH abuse mice model. METH (1 mg/kg/day, i.p.) was injected into C57BL/6 mice for four alternative days, and a conditioned place preference (CPP) test was performed. The METH-administered group exhibited increased sensitivity to place preference and significantly decreased levels of dopamine-related markers such as dopamine 2 receptor (D2R) and tyrosine hydroxylase in the striatum of the mice. Moreover, METH caused apoptotic cell death by induction of inflammation and oxidative stress. Conversely, APN treatment (3 and 10 mg/kg, i.p.) significantly reduced METH-mediated place preference and restored the levels of D2R and tyrosine hydroxylase in the striatum. APN increased the anti-apoptotic Bcl-2 to pro-apoptotic Bax ratio and decreased the expression of inflammatory protein Iba-1. METH-induced lipid peroxidation was effectively mitigated by APN by up-regulation of antioxidant enzymes such as manganese-superoxide dismutase and glutamylcysteine synthase via activation of nuclear factor-erythroid 2-related factor 2. These results suggest that APN may have protective potential and be considered as a promising therapeutic agent for METH-induced drug addiction and neuronal damage.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2018년도 추계학술대회
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• pp.123-123
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• 2018

Premenstrual syndrome (PMS) is a common disorder affecting the emotional and physical health of women during certain periods of the menstrual cycle. Many researchers who have previously studied PMS have believed that PMS is associated with changes in sex hormones and serotonin levels at the beginning of the menstrual cycle. However, recent studies suggest that progesterone/estrogen imbalance and elevation of prolactin-induced by dopamine low-secretion play a crucial role in increasing PMS symptoms. Because of this, we have focused on mitigating PMS symptoms through the mechanism of prolactin secretion inhibition by dopamine receptor activation. The inhibition of prolactin secretion by 61-kinds of medicinal herb extracts was investigated in GH3 pituitary cells. Among them, Inula heleniun L. root extract (IHE) showed excellent prolactin secretion inhibitory effect. IHEs were prepared using 30, 50, and 70% ethanol. And the yield, cytotoxicity, dopamine receptor activity and inhibition of prolactin secretion of each extract were measured. Through a series of experiments, we found that prolactin secretion was significantly reduced (P<0.01) by the components present in IHE and that dopamine receptor regulation was possible (P<0.05). Considering yield and safety, we suggest the use of 30% ethanol IHE in the development of PMS symptom relief products.

• 약학회지
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• 제47권4호
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• pp.230-233
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• 2003

Previously, protoberberine alkaloids such as berberine and palmatine have been found to lower dopamine content in PC12 cells (Shin et at., 2000). In this study, the effects of berberine and palmatine on L-DOPA-induced increase in dopamine level and cytotoxicity in PC12 cells were investigated. Treatment of PC12 with L-DOPA at concentration ranges of 20∼50 $\mu$M increased dopamine content and the increase in dopamine levels by L-DOPA was inhibited by 10∼40 $\mu$M berberine and 10∼80 $\mu$M palmatine, which the concentration ranges did not show a cytotoxicity. However, berberine and palmatine at concentrations higher than 50 $\mu$M and 100 $\mu$M caused a cytotoxicity, respectively. In addition, berberine (10∼20 $\mu$M) and palmatine (10∼50 $\mu$M) at non-cytotoxic concentration ranges aggravated L-DOPA-induced cytotoxicity in PC12 cells (L-DOPA concentration ranges, 20∼50 $\mu$M). The L-DOPA-induced cytotoxicity was also significantly potentiated by berberine (50 $\mu$M) and palmatine (100 $\mu$M) with cytotoxic ranges. These data demonstrate that berberine and palmatine inhibit L-DOPA-induced increase in dopamine content and stimulate L-DOPA-induced neurotoxicity. Therefore, the possibility that the long-term L-DOPA treated patients with berberine and palmatine could be checked the adverse symptoms.

• 동의생리병리학회지
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• 제20권5호
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• pp.1149-1154
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• 2006

Repeated administration of all addictive drugs, including nicotine, can produce sensitization of extracellular dopamine levels in the nucleus accumbens and behavioral sensitization in rat, as evidenced by an enhanced locomotor response and increased dopamine release in brain to a subsequent injection of the drug. In order to investigate the effect of Zizyphus jujuba extract on repeated nicotin-induced sensitization, rats were given repeated injection of saline or nicotine (0.4 mg/kg s.c., twice a day for 7 d), followed by one challenge injection on the 4th day after the last daily injection. Systemic challenge with nicotine (0.4 mg/kg s.c.) and a direct local challenge of 3 mM a larger increase in locomotor activity and extracellular dopamine release in the nucleus accumbens in nicotine-pretreated rats than in saline-pretreated rats, respectively. Zizyphus jujuba extract significantly decreases locomotor activitiy and dopamine release in the nucleus accumbens induced by a nicotine challenge. These results suggest that Zizyphus jujuba extract may attenuate nicotine-induced neurochemical and behavioral sensitization and may be effective in suppressing compulsive nicotine-seeking behavior.

• Biomolecules & Therapeutics
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• 제31권1호
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• pp.108-115
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• 2023

Numerous psychotropic and addictive substances possess structural features similar to those of β-phenethylamine (β-PEA). In this study, we selected 29 β-PEA derivatives and determined their structure-activity relationship (SAR) to their ability to inhibit dopamine (DA) reuptake; conducted docking simulation for two selected compounds; and identified their potential functionals. The compounds were subdivided into arylethylamines, 2-(alkyl amino)-1-arylalkan-1-one derivatives and alkyl 2-phenyl-2-(piperidin-2-yl)acetate derivatives. An aromatic group, alkyl group, and alkylamine derivative were attached to the arylethylamine and 2-(alkyl amino)-1-arylalkan-1-one derivatives. The inhibitory effect of the compounds on dopamine reuptake increased in the order of the compounds substituted with phenyl, thiophenyl, and substituted phenyl groups in the aromatic position; compounds with longer alkyl groups and smaller ring-sized compounds at the alkylamine position showed stronger inhibitory activities. Docking simulation conducted for two compounds, 9 and 28, showed that the (S)-form of compound 9 was more stable than the (R)-form, with a good fit into the binding site covered by helices 1, 3, and 6 of human dopamine transporter (hDAT). In contrast, the (R, S)-configuration of compound 28 was more stable than that of other isomers and was firmly placed in the binding pocket of DAT bound to DA. DA-induced endocytosis of dopamine D₂ receptors was inhibited when they were co-expressed with DAT, which lowered extracellular DA levels, and uninhibited when they were pretreated with compound 9 or 28. In summary, this study revealed critical structural features responsible for the inhibition of DA reuptake and the functional role of DA reuptake inhibitors in regulating D₂ receptor function.

• 대한약리학회지
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• 제30권1호
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• pp.39-48
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• 1994

포만중추 (satiety center)를 자극하여 음식섭취를 억제한다고 알려진 CCK-8을 흰쥐 복강에 투여하여, 흰쥐 뇌의 도파민 변화에 대한 CCK-8의 효과를 관찰하였다. 흰쥐 뇌의 부위별 도파민 함량은 HPLC-ECD방법으로 측정하였으며, 시상하부와 흑질에서의 TH-immunoreactive neuron은 면역조직화학법과 영상분석법을 시행하였다. 굶긴 쥐에서는 정상 쥐에 비하여, 도파민 함량이 전두 피질, 해마, 시상하부 및 편도체에서 각각 감소하였다. CCK-8을 투여한 쥐는 정상 쥐와 굶긴 쥐에 비하여, 도파민 함량이 시상하부에서 의미있게 감소하였다. 또한 굶긴 쥐는 정상 쥐와 비교하여, TH-positive neuron의 분포와 수가 뇌실옆핵, 깔때기핵, 정중융기 및 혹질에서 현저히 감소하였다. CCK-8투여시, 시상하부와 흑질에서의 TH-immunoreactive neuron의 수는 굶긴 쥐에 비하여 증가하였다. 이상의 실험 결과로 보아 음식물 섭취를 억제하는 작용이 있는 CCK-8은 시상하부의 도파민 신경계와 일부분 관련되어 있으며, 또한 시상하부와 흑질에 존재하는 TH-positive neuron은 음식물 섭취 행위에 중요한 역할이 있음을 시사하고 있다.

• BMB Reports
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• 제43권9호
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• pp.593-598
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• 2010

Tetrahydrobiopterin ($BH_4$) is a pivotal cofactor for enzymes responsible for the synthesis and release of monoamine neurotransmitters including dopamine and serotonin as well as the release of glutamate. Deficiencies in $BH_4$ levels and reduced activities of $BH_4$-associated enzymes have been recently reported in patients with schizophrenia. Accordingly, it is possible that abnormalities in the biochemical cascades regulated by $BH_4$ may alter DA, 5-HT and Glu neurotransmission, and consequently contribute to the pathophysiology of different neuropsychiatric diseases including schizophrenia. The development of a novel strain of mutant mice that is deficient in $BH_4$ by knocking out the expression of a functional sepiapterin reductase gene (spr -/-) has added new insights into the potential role of $BH_4$ in the pathophysiology and improved treatment of schizophrenia.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.79.3-80
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• 2003

The effects of anonaine, an aporphine isoquinoline alkaloid, on dopamine biosynthesis and L-DOPA-induced neurotoxicity in PC12 cells were investigated. Treatment of PC12 cells with 0.05 ${\mu}$M anonaine showed a significant inhibition of dopamine content. The IC$\sub$50/ value of anonaine was 0.05 ${\mu}$M. Under the same conditions, 0.05 ${\mu}$M anonaine also inhibited tyrosine hydroxylase (TH) activity at 24 h (62.0% inhibition of the control level). TH mRNA levels were also decreased by the treatment with anonaine. (omitted)