• Toxicological Research
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• v.26 no.4
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• pp.315-320
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• 2010

It has been clinically reported that toluene causes mental depression in humans. However, the detrimental effects of toluene exposure on brain function and the relation between features of mental depression and toluene exposure are poorly understood. This study evaluated depression-like behaviors in adult C57BL/6 mice after administration of toluene, and elucidated the effects of classical antidepressants on the depression-like behaviors. For the estimation of depression-like behaviors, tail suspension test (TST) and forcedswim test (FST) were performed 1, 4 and 16 days after toluene (0~1000 mg/kg bw) treatment. In addition, classical antidepressants such as fluoxetine (FLX, 20 mg/kg bw) and imipramine (IMI, 40 mg/kg bw) were administered 12 h and 1 h before the tests. In the TST and FST, toluene-treated mice exhibited a longer duration of immobility than vehicle-treated mice 1 and 4 days after toluene treatment. The depression-like behaviors were significantly reversed by FLX and IMI. The weight of the adrenal gland and the size of adrenocortical cells were significantly higher in toluene-treated mice compared to vehicle-treated controls. It is suggested that acute toluene exposure of adult mice is sufficiently detrimental to induce depression. In addition, this study has established a mouse model for a depressive state induced by toluene treatment.

• Sleep Medicine and Psychophysiology
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• v.2 no.1
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• pp.23-30
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• 1995

Bedwetting is the most common urologic complaint among children. Wetting frequency decreases from birth to adolescence. Etiology is multifactorial : genetic, neuromuscular or urologic maturation, psychosocial stressors, toilet training, or biologic aspects. Treatment has been also multimodal : drugs to depress bladder activity, increase urethral resistance, or modulate sleep. and recently urine reduction modulation. All of these approaches reflect a lack of sufficient knowledge of the underlying pathophysiology of nocturnal enuresis. Recent researches have focused on sleep disturbances, bladder reservoir function, urine output, and a combination of the three. Sleep studies indicate that enuretic patients are normal sleepers, and enuresis can take place during any stage of sleep, but generally occurs when the bladder is filled to the equivalent of maximal daytime functional capacity. Bladder reservior capacity appears to be normal, and bladder instability is somewhat related with the pathology of nocturnal enuresis. However, enuretic patients have shown the lack of normal nocturnal increase in antidiuretic hormone levels, and nocturnal urine production increases up to 2-4 times volume of functional bladder capacity, which explains the need for bladder emptying. But behavioral approaches, especially Bell-alarm method, remain important in the treatment of primary enuresis.

• Korean Journal of Veterinary Research
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• v.39 no.1
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• pp.62-69
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• 1999

Although it has been reported that hormones or chemicals, which increase in intracellular cAMP, produced $Mg^{2+}$ release from the heart, it is not well characterized whether a specific $Mg^{2+}$ exchanger is involved in cAMP-induced $Mg^{2+}$ efflux in the mammalian hearts. In this work, we studied the relationship between the increase in intracellular cAMP and ion transport system on $Mg^{2+}$ regulation in the perfused rat heart and isolated myocytes. The $Mg^{2+}$ content in the perfusate and supernatant were measured by atomic absorption spectrophotometer. The addition of membrane permeable cAMP analogue to the perfused hearts and myocytes induced a $Mg^{2+}$ efflux in the dose dependent manners. $Mg^{2+}$ efflux was stimulated by cAMP modulators (forskolin, IBMX and Ro20-1724) in the perfused hearts and myocytes. cAMP-induced $Mg^{2+}$ efflux was inhibited by $H_7$, benzamil or imipramine in the perfused hearts and myocytes, but not by EIPA. We confirmed that a significant $Mg^{2+}$ efflux was induced by an increase in intracellular cAMP in the hearts and myocytes. The cAMP-induced increase of $Mg^{2+}$ efflux in the hearts may be involved in ion transport system ($Na^+-Ca^{2+}$ and $Na^+-Mg^{2+}$ exchanger).

• Journal of Pharmacopuncture
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• v.21 no.1
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• pp.35-40
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• 2018

Objective: The role of BDNF (brain-derived neurotrophic factor), CREB (cAMP response element binding) and VGF neuropeptide has been proved in antidepressant activity of long term saffron administration in the rat hippocampus. In this study we evaluated the role of these proteins in antidepressant activity of saffron in long term administration in the rat cerebellum. Methods: Saffron aqueous extract (40 and 80 mg/kg/day) and imipramine (10 mg/kg/day) were administered intraperitoneally for 21 days to rats. At the end of experiment, animals were sacrificed and cerebellums were separated. The protein levels of BDNF, VGF, CREB and P- CREB in the rat cerebellum were evaluated using western blot analysis. Results: Saffron aqueous extract (80mg/kg/day) caused significant increase in protein level of P-CREB in long term treatment in the rat cerebellum. The increases in the protein levels of VGF, CREB and BDNF were not significant. Conclusion: In summary, our results showed that antidepressant effect of saffron in rat cerebellum might be due to the enhanced phosphorylation of CREB.

• Korean Journal of Veterinary Research
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• v.39 no.3
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• pp.463-471
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• 1999

Magnesium($Mg^{2+}$) is one of the most abundant intracellular divalent cation. Although recent studies demonstrate that adrenergic receptor stimulation evokes marked changes in $Mg^{2+}$ homeostasis, the regulation of $Mg^{2+}$ by dopaminergic receptor stimulation is not yet known. In this work, we used dopaminergic agents to identify which type(s) of receptors were involved in the mobilization of $Mg^{2+}$ by dopaminergic receptor stimulation in the perfused rat hearts, isolated myocytes and circulating blood. The $Mg^{2+}$ content was measured by atomic absorbance spectrophotometry. Dopamine(DA), apomorphine(APO) and pergolide stimulated $Mg^{2+}$ efflux in the perfused rat hearts and these effects were inhibited by haloperidol or fluphenazine, nonselective dopaminergic antagonists. SKF38393, a selective doparminergic agonist, increased $Mg^{2+}$ efflux from the perfused hearts in dose dependant manners and SKF38393-induced $Mg^{2+}$ efflux was blocked by haloperidol. However, dopaminergic agonists-induced $Mg^{2+}$ efflux was potentiated in the presence of sulpiride or eticlopride, $D_2$-selective antagonist, from the perfused hearts. This increase of $Mg^{2+}$ efflux was blocked by haloperidol or imipramine. DA or pergolide increased in circulating $Mg^{2+}$ from blood. By contrast, PPHT stimulated $Mg^{2+}$ influx(a decrease in efflux) from the perfused hearts and circulating blood. PPHT-induced $Mg^{2+}$ influx was blocked by fluphenazine in the perfused hearts. DA-stimulated $Mg^{2+}$ efflux was inhibited by dopaminergic antagoinst in the isolated myocytes. In conclusion, the flux of $Mg^{2+}$ is modulated by DA receptor activation in the rat hearts. The efflux of $Mg^{2+}$ can be increased by $D_1$-receptor stimulation and decreased by $D_2$-receptor stimulation, respectively.

• YAKHAK HOEJI
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• v.57 no.4
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• pp.289-292
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• 2013

A total of 2,080 forensic autopsies in Seoul, Incheon and Gyeonggi province were performed by the National Forensic Service (NFS) in 2010. After analysing blood samples collected at autopsies by GC-MS and LC-MS/MS, the types and prevalence of drugs and poisons in blood were investigated using our laboratory information management system. Among 2,080 cases, 1,061 cases (51%) were positive for drugs and poisons. Surprisingly, antidepressants were identified in 137 cases which comprised 13% of the positive cases. Twelve different kinds of antidepressants were determined: Amitriptyline, fluoxetine, nortriptyline, trazodone, imipramine, mirtazapine, citalopram, venlafaxin, clomipramine, paroxetine, sertraline and bupropion. Amitriptyline was the most frequently detected antidepressant and was identified in 39 cases. Moreover, amitriptyline, fluoxetine, and nortriptyline were included in the list of the 20 most commonly encountered drugs or poisons in the analysis of blood collected at autopsies from 2007 to 2009, indicating the prevalence of their use. In this study, the 137 antidepressant-related deaths were classified by the mode of death to predict the prevalence of these drugs. As a result, those deaths were divided into four groups based on the cause and mode of death: 56 cases of suicide with fatal concentrations of antidepressant drugs in blood, 6 homicidal cases directly or indirectly related to antidepressants, 59 natural deaths with antidepressants detected in blood and 16 deaths caused by fire or other accidents with antidepressants detected in blood. Because incidents involving antidepressants have been increasing, especially in suicides or homicides, it is necessary for the health authorities and law enforcement administrations to cooperate and share the statistical data for curbing the abuse of antidepressants. This report is expected to provide the reference data related with antidepressants for the investigation of the deaths.

• YAKHAK HOEJI
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• v.39 no.2
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• pp.161-168
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• 1995

Brain dopamine systems play a central role in the control of movement, hormone release, and many complex behavior. The action of dopamine at its synapse is terminated predominately by high affinity reuptake into presynaptic terminals by dopamine transporter (DAT). The dopamine transporter(DAT) is membrane protein localized to dopamine-containing nerve terminals and closely related with cocaine abuse, Parkinsonism, and schizophrenia. In present study, the recombinant plasmid pRc/CMV-DAT, constructed by subcloning of a cDNA encoding a bovine DAT into eukaryotic expression vector pRc/CMV, was stably transfected into CV-1 cells(monkey kidney cell line). The DAT activities in the cell lines selected by Geneticin$^{R}$ were determined by measuring the uptake of $[^3H]$-dopamine. The transfected cell lines showed 30-50 fold higher activities than untransfected CV-1 cell line, and this result implies that DAT is well expressed and localized in transfected cells. The transfected cells accumulated $[^3H]$-dopamine in a dose-dependent manner with a $K_{m}$ of 991.6nM. Even though high doses of norepinephrine, epinephrine, serotonin, and choline neurotransmitters inhibited the uptake of $[^3H]$-dopamine, DAT in transfected cell line was proven to be much more specific to dopamine. The psychotropic drugs such as GBR12909, CFT, normifensine, clomipramine, desipramine, and imipramine inhibited significantly the dopamine uptake in tissue culture cells stably transfected with DAT cDNA. Radioactive in situ hybridization was done to map the cellular localization of DAT mRNA-containing cells in the adult rat central nervous system. The strong hybridization signals were detected only in the substantia nigra pars compacta and ventral tegmental area. The restricted anatomical localization of DAT mRNA-containing cells confirms the DAT as a presynaptic marker of dopamine-containing cells in the rat brain.

• YAKHAK HOEJI
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• v.50 no.6
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• pp.429-435
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• 2006

The antidepressant effects of Cirsium japonicum compositae was investigated using open field test and forced swimming test. Total extract of Cirsium japonicum (CJ) was orally administered at dose of 20, 100, 300, 500 mg/kg bodyweight. Supplementation of CJ increased dose-dependently movement, rearing frequency and total turn angle in the center area of open field in mice. Treatment of Cirsium japonicum's extract (300 mg/kg, CJ) decreased immobile duration and increased mobile and strong mobile duration significantly; and it is comparable to that of imipramine and fluoxetine. These results indicate that CJ has antidepressant effect. Treatment of CJ did not induced any impairment in motor coordination and myorelaxation. These results indicate that the constituents or its complex of Cirsium japonicum could be a candidate of new antidepressant drug.

• Journal of Pharmacopuncture
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• v.22 no.2
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• pp.90-94
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• 2019

Objectives: Paclitaxel (PTX) as an anticancer drug used against solid cancers, possesses adverse reactions such as neuropathic pain which has confined its use. PTX-induced neuropathic pain is mediated via activation of oxidative stress. Berberine (BER), an isoquinoline phytochemical found in several plants, exerts strong antioxidant and painkilling properties. In the current study, we aimed to evaluate pain-relieving effect of BER in a mouse model of PTX-induced neuropathic pain. Methods: This study was done using 42 male albino mice that were randomly divided into 6 groups (n = 7) as follow: Sham-operated (not treated with PTX), negative control group (PTX-treated mice receiving normal saline), BER 5, 10, and 20 mg/kg (PTX-treated mice receiving BER) and positive control group (PTX-treated mice receiving imipramine 10 mg/kg). Neuropathic pain was induced by intraperitoneal administration of four doses of PTX (2 mg/kg/day) on days 1, 3, 5 and 7. Then, on day 7, hot plate test was done to assess latency to heat to measure possible anti-neuropathic pain effect of BER. Results: Four doses of PTX 2 mg/kg/day induced neuropathy that was reduced by BER at all time-points (i.e. 0, 30, 60, 90 and 120 min) after injection (P < 0.001 in comparison to control). The statistical analysis of data showed significant differences between groups (P < 0.001 in comparison to negative control), at 30, 60, 90 and 120 min after injection of BER 5, 10 and 20 mg/kg; in other words, 30, 60, 90 and 120 min after BER administration, neuropathic pain was significantly reduced as compared to normal saline-treated mice. Conclusion: Altogether, our results showed that PTX could induce neuropathic pain as reflected by hyperalgesia and BER could alleviate PTX-induced thermal hyperalgesia.

• The Korean Journal of Pharmacology
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• v.24 no.2
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• pp.165-178
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• 1988

In this study, the effect of single or repeated (daily for 7 or 14 days) electroconvulsive shock (ECS) on central and peripheral opiate system and modification of the actions of ECS by several psychoactive drugs were investigated in the rat. Repeated ECS caused increase of Met-enkephalin content and decrease of Bmax of specific $[^3H]$imorphine binding in the rat brain. These effects were persisted more than 7 days after the last ECS, but single ECS failed to show these effects. However, ${\beta}-endorphin$ content was decreased in midbrain preparation and increased in plasma by repeated or single ECS. These phenomenon was seen shortly after the last ECS. After ECS-induced seizure was prevented by phenobarbital, ECS-induced increase in Met-enkephalin content was significantly attenuated. Imipramine or pargyline did not affect the action of repeated ECS. On the other hand, reserpine, chlorpromazine or haloperidol which were classified as neuroleptic antipsychotics, augmented the ECS-induced changes of central and peripheral opiate parameters. Furthermore, in groups received repeated ECS, changes of Bmax of specific $[^3H]-morphine binding$ binding was inversely correlated with changes of Met-enkephalin contents, but not with changes of ${\beta}-endorphin$ contents. From these results, it is inferred that the central or peripheral opioidergic system may be involved in the therapeutic and/or adverse effects of ECS which also can be influenced by some psychoactive drugs.