• The Korean Journal of Physiology and Pharmacology
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• v.4 no.5
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• pp.355-359
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• 2000

Cocaine induces immediate early gene expression and behavioral changes by blocking dopamine transporters in the terminals of nigrostriatal neurons in the striatum. The pharmacological role of serotonin 2/1C (5HT2/1C) receptors in cocaine-induced expression of zif268 (NGFI-A, egr1 and Krox-24) mRNA, a member of the zinc finger, was investigated using quantitative in situ hybridization histochemistry in vivo. Behavioral alterations induced by cocaine were also monitored in relation with blockade of the receptors. Systemic injection of ritanserin (1 mg/kg, s.c.), a 5HT2/1C receptor antagonist, did not reverse behavioral alterations and zif268 mRNA gene expression induced by 15 mg/kg cocaine, i.p., in the dorsal and ventral striatum. These data indicate that ritanserin-sensitive 5HT2/1C receptors are not necessary for cocaine-induced behavioral alterations and zif268 mRNA gene expression in the striatum.

• Korean Journal of Biological Psychiatry
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• v.17 no.4
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• pp.177-193
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• 2010

Significant advances have been made in understanding the biological underpinnings of post-traumatic stress disorder(PTSD), particularly in the field of genetics and neuroimaging. Association studies in candidate genes related with hypothalamic-pituitary-adrenal axis, monoamines including serotonin, dopamine and noradrenaline, and proteins including FK506-binding protein 5 and brain-derived neurotrophic factor have provided important insights with regard to the vulnerability factors in PTSD. Genome-wide association studies and epigenetic studies may provide further information for the role of genes in the pathophysiology of PTSD. Hippocampus, medial prefrontal cortex, anterior cingulated cortex and amygdala have been considered as key structures that underlie PTSD pathophysiology. Future research that combines genetic and neuroimaging information may provide an opportunity for a more comprehensive understanding of PTSD.

• The Korean Journal of Pain
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• v.27 no.2
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• pp.103-111
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• 2014

Nefopam (NFP) is a non-opioid, non-steroidal, centrally acting analgesic drug that is derivative of the nonsedative benzoxazocine, developed and known in 1960s as fenazocine. Although the mechanisms of analgesic action of NFP are not well understood, they are similar to those of triple neurotransmitter (serotonin, norepinephrine, and dopamine) reuptake inhibitors and anticonvulsants. It has been used mainly as an analgesic drug for nociceptive pain, as well as a treatment for the prevention of postoperative shivering and hiccups. Based on NFP's mechanisms of analgesic action, it is more suitable for the treatment of neuropathic pain. Intravenous administration of NFP should be given in single doses of 20 mg slowly over 15-20 min or with continuous infusion of 60-120 mg/d to minimize adverse effects, such as nausea, cold sweating, dizziness, tachycardia, or drowsiness. The usual dose of oral administration is three to six times per day totaling 90-180 mg. The ceiling effect of its analgesia is uncertain depending on the mechanism of pain relief. In conclusion, the recently discovered dual analgesic mechanisms of action, namely, a) descending pain modulation by triple neurotransmitter reuptake inhibition similar to antidepressants, and b) inhibition of long-term potentiation mediated by NMDA from the inhibition of calcium influx like gabapentinoid anticonvulsants or blockade of voltage-sensitive sodium channels like carbamazepine, enable NFP to be used as a therapeutic agent to treat neuropathic pain.

• Archives of Pharmacal Research
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• v.22 no.2
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• pp.113-118
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• 1999

Previous work in our laboratory has shown that the N-methyl-D-aspartate (NMDA) receptor antagonists, AP-5, CPP, MK-801, ketamine, dextrorphan and dextromethorphan cause a pronounced enhancement of 5-hydroxytryptamine (5-HT)-induced head-twitch response (HTR) in intact mice, suggesting the involvement of NMDA receptors in the glutamatergic modulation of serotonergic function at the postsynaptic $5-HT_{2}$ receptors. The purpose of this study was to extend our previous work on the behavioral interaction between glutamatergic and serotonergic receptors. In the present study, both competitive (AP-5 and CPP) and noncompeti-tive (MI-801, ketamine, dextrorphan and dextromethorphan) NMDA receptor antagonists markedly enhanced 5-HT-induced selective serotonergic behavior, HTR, in p-chlorophenylalanine (PCPA)-treated mice which were devoid of any involvement of indirect serotonergic function, to establish the involvement of the NMDA receptor in 5-HT-induced HTR at the postsyaptic $5-HT_{2}$receptors. In addition, the enhancement of 5-HT-induced HTR was inhibited by a dopamine agonist, apomorphine, NMDA receptor antagonist, NMDA and a serotonin $5-HT_{2}$receptor antagonist, cyproheptadine, in PCPA-treated mice. Therefore, the present results support our previous conclusion that the NMDA receptors play an important role in the glutamatergic modulation of serotonergic function at the poststynaptic $5-HT_{2}$ receptors.

• The Korean Journal of Pharmacology
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• v.20 no.1 s.34
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• pp.33-39
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• 1984

The present study was undertaken to elucidate the chracteristics in behavioral changes of chronic doses of methamphetamine on open-field activity in rats. On the other hand, the nucleus accumbens septi(NAB), one of the major areas containing mesolimbic dopaminergic terminals, has been considered to be an important site of action for dopaminergic agonists. Therefore, it also designed to investigated influence of NAB lesions. on behavioral effects of chronic-methamphetamine. Caudal and rostral areas of NAB(cr-NAB) were lesioned by applying DC of 3.0 mA for 15 sec., simultaneously. The results were as follows: 1) The rats exhibited hyperactivity after chronic administration of methamphetamine 2) The cr-NAB-lesioned rats showed a significant increase in locomotor activity only at 2 days after NAB lesions 3) Methamphetamine-induced hyperactivity was significantly decreased in the NAB-lesioned rats, and stereotyped behavior was induced instead by the drug. 4) Dopamine content of striatum was significantly decreased and serotonin content of olfactory bulb was significantly increased in NAB-lesioned rats. These results suggest that NAB plays an important role in locomotor activity and methamphetamine-induced hyperactivity.

• YAKHAK HOEJI
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• v.54 no.4
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• pp.300-308
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• 2010

Adrenoceptor has been considered to be an important target in psychiatric disorders. Based on x-ray structures of bovine rhodopsin, we established homology model of ${\alpha}_{2c}$-adrenoceptor (ADA2C_rat) and then analyzed docking from binding model of receptor-ligand complex with high-active compound No.29 in tricyclic isoxazole analogues (1-30). We observed that the N (1.907 $\AA$) and O (1.712 $\AA$) atoms of isoxazole ring on the docked ligand (No.29) formed H-bonding interaction with O-H of Ser5.32 and carmeron phenyl ring centroid of tricyclic isoxazole formed $\pi-\pi$ interaction at 3.342 $\AA$ distance with phenyl ring centroid of Phe6.52. According to predictions of blood-brain distribution (logBB) through penetration of blood-brain barrie (BBB) and polar surface area (PSA) of the ligands, the high-active compound No.29 has values of logBB=-0.203, PSA=67.50, respectively. These results suggest that the high-active compound No.29 is a novel anti-depressant with the characteristics such as dopamine and serotonin.

• Herbal Formula Science
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• v.17 no.2
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• pp.143-150
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• 2009

The effects of aqueous extract of Schizandrae Fructus (AESC) on lead (Pb)-induced changes of monoamine neurotransmitters in the hippocampus (HIP) of adult rats were investigated. Male Sprague-Dawley rats were received intraperitoneal (i.p.) administration of Pb acetate (5 mg/kg/d) for 28 days and sacrificed 7 days after the last administration. Concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA) in HIP were measured by HPLC. There were significant decreases of NE, DA, 5-HT and 5-HIAA in Pb treated rats (P < 0.05), while pretreatment with AESC (100 mg/kg/d or 300 mg/kg/d, p.o., 2 h before Pb) greatly inhibited the decrease of monoamine transmitters, respectively (P < 0.05). Also, AESC (300 mg/kg/d) significantly increased the reduction of glutathione contents and superoxide dismutase activities in HIP induced by chronic Pb. These results suggest that AESC ameliorates Pb-induced depletion of monoamine neurotransmitters in HIP through its antioxidant activity.

• Journal of Sasang Constitution and Immune Medicine
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• v.27 no.2
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• pp.270-287
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• 2015

Objectives To evaluate the neuroprotective effects of modified Yuldahanso-tang (MYH) in a Parkinson's disease mouse model. Methods 1) Four groups (each of 8 rats per group) were used in this study. 2) The neuroprotective effect of MYH was examined in a Parkinson's disease mouse model. C57BL/6 mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg/day), intraperitoneal (i.p.) for 5 days. 3) The brains of 2 mice per group were removed and frozen at $-20^{\circ}C$, and the striatum-substantia nigra part was seperated. The protein volume was measured by Bradford method following Bio-Rad protein analyzing kit. Using mouse/Rat Dopamine ELISA Assay Kit. 4) The brains of 2 mice per group were separated and removed. TH-immunohistochemical was examined in the MPTP-induced Parkinson's disease mice to evaluate the neuroprotective effects of MYH on ST and SNpc. 5) Two mice out of each group were anesthetized and skulls were opened from occipital to frontal direction to take out the brains. The brains added TTC solution for 20 minutes for staining. 6) The water tank used for morris water maze test was filled with $28^{\circ}C$ water, and a round platform of 10cm in diameter was installed for mice to step on. The study was carried out once a day within 30 seconds, keep exercising to step on the platform in the pool. 7) The brains of two mice out of each group were fixed in 10% formaldehyde solution and paraphillin substance was infiltrated. They were fragmented by microtome, and observed under an optical microscope after Hematoxylin & Eosin staining. 8) A round acrylic cylinder with its upper side open was filled with clean water and depressive mouse models were forced to swim for 15 minutes. After 24 hours the animals were put in the same equipment for 5 minutes and were forced to swim. 9) The convenient, simple, and accurate high-performance liquid chromatography (HPLC) method was established for simultaneous determination of Neurotransmitters in MPTP-MYH group. Results 1) MYH possess Dopamine cell protective effect on MPTP-induced injury in striatum and substantia nigra pars compacta. 2) MYH inhibits the loss of tyrosine hydroxylase-immunoreacitive (TH-IR) cells in the striatum and substantia nigra pars compacta on MPTP-induced injury in C57BL/6 mice. 3) MYH possesses improvement effect on MPTP-induced memory deterioration in C57BL/6 mice through the reduction of prolongated Sort of lost time by MPTP injection using the Morris water maze test. 4) MYH possesses hippocampal neuron protective effect on MPTP-induced injury in C57BL/6 mice. 5) MYH possesses improvement effect on MPTP-induced motor behaviour deficits and depression in C57BL/6 mice through the reduction of prolongated losing motion by MPTP injection using the Forced swimming test. 6) MYH increases serotonin product amount on MPTP-induced injury in C57BL/6 mice. Conclusions This experiment suggests that the neuroprotective effect of MYH is mediated by the increase in Dopamin, TH-ir cell, Hippocampus and Serotonin. Furthermore, MYH essential oil may serve as a potential preventive or therapeutic agent regarding Parkinson's disease.

• 한국체육학회지인문사회과학편
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• v.55 no.2
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• pp.603-615
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• 2016

This study was conducted by performing intensities aerobic exercise for 12 weeks, three times a week targeting 28 middle aged women. The purpose of this study was analyzing factors which affect cognitive function and changes of blood pressure, renin-aldosterone system, neurotransmitter, cognitive function and working memory after treatment. The participants were divided into three groups which are the control group(n=9, non exercise), moderate intensity aerobic exercise group(n=10, 50%V02max), high intensity aerobic exercise group(n=9, 70%V02max). The two-way ANOVA(repeated measure) and multiple regression analysis were carried out to target those three groups before and after treatment. The results were as follows like this. The moderate intensity aerobic exercise increased renin, brain derived neurotrophic factor(BDNF), cognitive function and working memory. Also, it reduced aldosterone, angiotensinII and aldosterone-renin ratio. The high intensity aerobic exercise showed increase BDNF, cognitive function and working memory and decrease systolic. As a result of a multiple regression analysis of factors affecting cognitive function after intensities aerobic exercise, the moderate intensity aerobic exercise affected diastolic blood pressure, decrease of aldosterone-renin ratio and working memory. Also, an increase of BDNF affected cognitive function, the high intensity aerobic exercise affected working memory BDNF and an increase of serotonin affected cognitive function. Therefore, It could be seen that more than moderate intensity exercise increase woman's cognitive function and working memory. Also, there were metabolic factors which affect the increase of cognitive function. To moderate intensity exercise, renin-aldosterone and working memory affected to increase of cognitive function. For high intensity exercise, BDNF and working memory affected to it.

• Biomolecules & Therapeutics
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• v.22 no.6
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• pp.558-562
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• 2014

Tramadol is an opioid analgesic agent that has been the subject of a series of case reports suggesting potential for misuse or abuse. However, it is not a controlled substance and is not generally considered addictive in Korea. In this study, we examined the dependence potential and abuse liability of tramadol as well as its effect on the dopaminergic and serotonergic systems in rodents. In animal behavioral tests, tramadol did not show any positive effects on the experimental animals in climbing, jumping, and head twitch tests. However, in the conditioned place preference and self-administration tests, the experimental animals showed significant positive responses. Taken together, tramadol affected the neurological systems related to abuse liability and has the potential to lead psychological dependence.