• Toxicological Research
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• 제26권4호
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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.

• 수면정신생리
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• 제2권1호
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• pp.23-30
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• 1995

유뇨증은 발병기전이 단일한 원인으로 설명되기 어려운 임상적으로 복합적인 질병이다. 유전적 요인, 신경근육계 및 비뇨기계의 미성숙, 심리사회적 요인이나 대소변 가리기 훈련의 이상, 그리고 생물학적 요인 등 여러 가지 원인론들이 있으나 아직 확실한 것은 없다. 그러나 최근 신경생리학적 연구와 신경 내분비학적 연구들의 결과, 야뇨증과 수면주기와의 관련성이나 야간의 항이뇨호르몬 (antidiuretic hormone) 분비 저하와의 관련성 등 보고되어 야뇨증의 치료에 있어 새로운 접근을 가능하게 하고 있다. Vasopressin 이 우수한 치료율, 안전성, 적은 부작용 등으로 새로운 치료약물로서 시도되고 있으나 재발율이 높아, imipramine또는 vasopressin의 투여와 Bell-alarm행동요법을 병행하여 치료하는 것이 바람직하다.

• 대한수의학회지
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• 제39권1호
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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).

• 대한약침학회지
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• 제21권1호
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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.

• 대한수의학회지
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• 제39권3호
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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.

• 약학회지
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• 제57권4호
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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.

• 약학회지
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• 제39권2호
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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.

• 약학회지
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• 제50권6호
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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.

• 대한약침학회지
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• 제22권2호
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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.

• 대한약리학회지
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• 제24권2호
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• pp.165-178
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• 1988

백서에서 전기충격 (electroconvulsive shock; ECS)이 뇌내 및 혈중 opiate system에 미치는 효과와 이에 대한 수종의 psychoactive drugs의 영향을 검토코저 1일 1회씩, 1, 3, 7및 14일간 ECS를 가하거나, 14일간 상기 약물과 ECS를 병행처리한 백서의 뇌내 specific $[^3H]$-morphine binding, Met-enkephalin 함량, ${\beta}-endorphin$ 함량 또는 혈중 ${\beta}-endorphin$ 농도를 측정하여 다음과 같은 결과를 얻었다. 1. 뇌내 Met-enkephalin의 함량은 1회의 ECS에 의해서 증가되는 경향을 보였으며 장기간의ECS를 가한 군에서는 최종 ECS 1시간 후부터 유의하게 증가되어 7일후까지 지속되었다. 2. 뇌내 ${\beta}-endorphin$의 함량은 ECS처리 횟수에 관계없이 최종 ECS 1시간후에는 유의하게 감소되었으나 24시간, 3일, 7일 및 14일후의 측정치는 대조군과 차이가 없었다. 3. 혈중 ${\beta}-endorphin$의 농도는 ECS처리 친수에 관계없이 최종 ECS 5분후에 유의하게 증가되었으나 1시간, 24시간, 7일 및 14일후의 측정치는 대조군과 차이가 없었다. 4. 뇌내 specific $[^3H]$-morphine binding의 Bmax는 1회의 ECS에 의해 변동되지 않았으나 장기간의 ECS를 가한 군에서는 ECS 1시간후부터 유의하게 감소되어 7일후까지 지속되었다. 한편 Kd치는 모든 실험군에서 변동되지 않았다. 5. ECS장기처리군에서 ECS 30분전 phenobarbital(100 mg/kg) 전처리는 ECS에 의한 뇌내Met-enkephalin함량증가를 현저히 억제 하였으며, ECS에 의한 뇌내 specific $[^3H]$-morphine binding의 Bmax감소, 뇌내 ${\beta}-endorphin$ 함량감소와 혈중 ${\beta}-endorphin$ 농도증가에 대해서는 영향을 주지 못하였다. 6. Imipramine 또는 pargyline 장기처리는 자체로써 뇌내 ${\beta}-endorphin$함량증가, 혈중 ${\beta}-endorphin$ 농도증가, 뇌내 specific $[^3H]$-morphine binding의 Bmax감소를 일으켰으나 뇌내 Met-enkephalin의 함량과 ECS작용에 영향을 미치지 못했다. 7. Reserpine, chlorpromazine 또는 haloperidol 장기처리는 자체로써 뇌내 Met-enkephalin의 함량증가, 뇌내 ${\beta}-endorphin$함량증가, 혈중 ${\beta}-endorphin$ 농도증가, 뇌내 specific $[^3H]$-morphine binding의 Bmax감소를 일으켰고, ECS효과를 강화시켰다. 8. 장기간 ECS를 가한 백서의 뇌내 specific $[^3H]$-morphine binding의 Bmax는 뇌내 Met-enkephalin 함량과는 유의한 역상관 관계를 보이 나 뇌내 ${\beta}-endorphin$ 함량과는 관계 가 없었다. 이상의 실험성적은 전기충격요법이 생체내에서의 작웅기전에 중추 또는 말초 opiate계가 개입되어 있음을 시사하며 또한 ECT의 효과가 수종의 중추신경계에 작용하는 약물에 의해 변동될수 있음을 보여준다.