• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.190-190
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• 2002

Methamphetamine (META) is a psychostimulant and has become popular recreational drug of abuse in many countries. The neurotoxic damage caused by METH is characterized by degeneration of the dopaminergic and serotonergic systems in striatum and hippocampus.(omitted)

• Biomolecules & Therapeutics
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• 제28권5호
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• pp.381-388
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• 2020

Methamphetamine (METH) is a highly addictive psychostimulant and one of the most widely abused drugs worldwide. The continuous use of METH eventually leads to drug addiction and causes serious health complications, including attention deficit, memory loss and cognitive decline. These neurological complications are strongly associated with METH-induced neurotoxicity and neuroinflammation, which leads to neuronal cell death. The current review investigates the molecular mechanisms underlying METH-mediated neuronal damages. Our analysis demonstrates that the process of neuronal impairment by METH is closely related to oxidative stress, transcription factor activation, DNA damage, excitatory toxicity and various apoptosis pathways. Thus, we reach the conclusion here that METH-induced neuronal damages are attributed to the neurotoxic and neuroinflammatory effect of the drug. This review provides an insight into the mechanisms of METH addiction and contributes to the discovery of therapeutic targets on neurological impairment by METH abuse.

• Biomolecules & Therapeutics
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• 제27권2호
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• pp.145-151
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• 2019

Methamphetamine (METH) acts strongly on the nervous system and damages neurons and is known to cause neurodegenerative diseases such as Alzheimer's and Parkinson's. Flavonoids, polyphenolic compounds present in green tea, red wine and several fruits exhibit antioxidant properties that protect neurons from oxidative damage and promote neuronal survival. Especially, epicatechin (EC) is a powerful flavonoid with antibacterial, antiviral, antitumor and antimutagenic effects as well as antioxidant effects. We therefore investigated whether EC could prevent METH-induced neurotoxicity using HT22 hippocampal neuronal cells. EC reduced METH-induced cell death of HT22 cells. In addition, we observed that EC abrogated the activation of ERK, p38 and inhibited the expression of CHOP and DR4. EC also reduced METH-induced ROS accumulation and MMP. These results suggest that EC may protect HT22 hippocampal neurons against METH-induced cell death by reducing ER stress and mitochondrial damage.

• 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.84.1-84.1
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• 2003

Methamphetamine is a powerful stimulant that appears to produce locomotor activity and behavioral sensitization. Previous study has indicated that dopaminergic receptors are implicated in the behavioral responses of methamphetamine. Recently, it has been reported that other receptors, especially, M1 muscarinic acetylcholine receptor (M1R) plays an important role in the regulation of behavioral responses, and this receptor is abundantly expressed in brain regions, including the cerebral cortex, striatum, and the hippocampus of the animal. (omitted)

• 감성과학
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• 제22권4호
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• pp.75-84
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• 2019

중독자들은 물질이나 행동과 같은 중독-관련 단서에 주의를 더 기울인다. 그리고 이러한 단서들에 증가된 주의는 갈망과 관련이 있다. 국내 마약류 사범 중 가장 많이 남용되고 있는 마약류는 메스암페타민이며, 재범률은 지속적으로 증가하고 있는 추세이다. 최근 3년 동안 전체 마약류 사범 중 여성의 비율은 21.1%이나, 여성 마약류 사범에 대한 연구의 부족으로 관련 정책과 심리치료 프로그램 개발을 위한 기초 자료는 부족한 실정이다. 본 연구의 목적은 여성 메스암페타민 중독자들을 대상으로 약물 단서에 대한 주의편향이 나타나는지를 확인하는 것이다. 본 연구에서는 교정기관에 수용중인 여성 메스암페타민 중독자(중독 집단) 22명과 약물과 관련한 문제가 없는 정상인(통제 집단) 22명을 대상으로 탐침탐사 과제를 수행하였다. 이 과제를 통해 약물 단서와 중성 단서 위치에 따른 정반응률 및 정반응시간을 산출하였다. 그 결과, 통제 집단은 정반응률과 정반응시간 모두에서 약물 단서와 중성 단서 간의 차이가 없었으나, 중독 집단은 중성단서에 비해 약물 단서에서 더 낮은 반응률과 더 느린 반응시간을 보였다. 이러한 본 연구의 결과는 마약류로부터 단절된 여성 메스암페타민 중독자들의 약물 단서에 대한 주의편향 특성을 규명하였다는 점에서 의의가 있다.

• 대한핵의학회지
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• 제39권6호
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• pp.481-488
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• 2005

목적: 도파민운반체의 기능적 영상술은 도파민 신경계의 시냅스전 신경말단의 상태를 나타내 줄 수 있어, 기저신경절을 침범하는 파킨슨 병 등의 진단 및 중증도 판단에 이용될 수 있으며, 도파민운반체가 코카인이나 methamphetamine 등 의존성 약물의 목표 부위이므로 이러한 약물의 남용자의 평가에 이용될 수 있다. 본 연구는 한국에서 생산된 도파민운반체 영상용 방사성의약품을 사용한 뇌 SPECT영상을 이용하여 methamphetamine 남용자에서 나타나는 소견과 이의 임상적 의의를 알아보고자 하였다. 대상 및 방법: Methamphetamine 남용자 6명 (남용자군, 전부 남자, 평균연령: $32{\pm}6.8$) 및 정상대조군 4명(대조군, 남:여=3:1, 평균연령=$44.0{\pm}14.7$세)을 대상으로 하였다. 남용자군 6명 모두에서 뇌 MRI가 시행되었다. 남용자군에서는 정신과적 증상과 우울증 증상을 정량적으로 평가하였다. 도파민운반체 영상은 I-123 IPT 185 MBq을 정맥 주사한 후 2시간에 삼중헤드 감마카메라(Prism 3000, Picker, USA)를 이용하여 뇌 SPECT 영상을 얻었다. 정성적인 판독과 함께, 정량적 분석으로 기저신경절 부위에 관심영역을 그려 기저신경절의 방사능량을 구하였고, 배후 방사능량은 후두엽 부위에 관심영역을 그려 방사능량을 구하였다. 기저신경절과 배후 방사능량을 이용하여 기저신경절 도파민운반체 특이결합/비특이결합 비율(특이결합비) (기저신경절방사능량-배후방사능량/배후방사능량)을 구하였다. 각군의 도파민운반체 특이겹합비를 비교하였으며, 남용자군에서는 정신과적 증상(Brief Psychiatric Rating Scale: BPRS) 및 우울증 증상 정도(Hamilton Depression Rrating Scale : HAMD)와 도파민운반체 특이겹합비의 상관성을 알아보았다. 결과: 남용자군 6명 모두는 뇌 MRI상 특이 소견이 관찰되지 않았으나, 모든 환자는 정신과적 증상과 우울증 증상을 나타내었으며 BPRS 점수와 HAMD 점수는 서로 밀접한 상관성을 보여 주었다(r=1.0, p=0.005). 남용자군의 I-123 IPT 뇌 SPECT의 정성적분석에서 5명(83.3%)이 기저신경절의 전체적 섭취가 불균등하고 미측의 섭취가 감소되어 비정상으로 판독 되었으며, 1명은 정상으로 판독되었다. 남용자군은 대조군에 비하여 낮은 기저신경절 도파민운반체 특이겹합비를 나타내었다($2.38{\pm}0.20\;vs\;3.04{\pm}0.27$, p=0.000) 남용자군의 BPRS 점수와 HAMD 점수가 높을수록 낮은 기저신경절 특이겹합비를 나타내어 역의 상관관계를 보였다(r=-0.908, p=0.012, r=-0.924, p=0.009). 결론: I-123 IPT뇌 SPECT는 흑질-선조체 도파민신경계의 손상을 일으키는 중증의 methamphetamine 남용자의 평가에 이용될 수 있다고 생각된다.

• Molecules and Cells
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• 제26권2호
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• pp.121-130
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• 2008

Methamphetamine, a commonly used addictive drug, is a powerful addictive stimulant that dramatically affects the CNS. Repeated METH administration leads to a rewarding effect in a state of addiction that includes sensitization, dependence, and other phenomena. It is well known that susceptibility to the development of addiction is influenced by sources of reinforcement, variable neuroadaptive mechanisms, and neurochemical changes that together lead to altered homeostasis of the brain reward system. These behavioral abnormalities reflect neuroadaptive changes in signal transduction function and cellular gene expression produced by repeated drug exposure. To provide a better understanding of addiction and the mechanism of the rewarding effect, it is important to identify related genes. In the present study, we performed gene expression profiling using microarray analysis in a reward effect animal model. We also investigated gene expression in four important regions of the brain, the nucleus accumbens, striatum, hippocampus, and cingulated cortex, and analyzed the data by two clustering methods. Genes related to signaling pathways including G-protein-coupled receptor-related pathways predominated among the identified genes. The genes identified in our study may contribute to the development of a gene modeling network for methamphetamine addiction.

• Archives of Pharmacal Research
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• 제20권1호
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• pp.46-52
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• 1997

To obtain more sensitive immunoassay for methamphetamine (MA) determination, the optimum condition of enzyme-linked immunosorbent assay (ELISA) was investigated in regard to immunogens, antibody purification methods and coating tracers. Activated MA, N-(4-aminobutyl)methamphetamine (4-ABMA), was conjugated with bovine serum albumin (BSA) or keyhole limpet hemocyanin (KLH) and used as immunogen. The antibodies were purified by protein G chromatography or various immunoaffinity chromatography-linked MA-protein ligands, such as MA-BSA, MA-KLH or MA-ovalbumin (OVA). Each purified antibody was characterized by means of sensitivity and cross-reactivity using the three MA-protein coating tracers, MA-BSA, MA-KLH and MA-OVA. The best sensitivity of each antibody was acquired with the MA-OVA tracer although the tracer concentration and the antibody titer level at optimum condition were varied. The antibody with high titer level did not always yield good sensitivity. At optimum condition, immunoaffinity chromatography-purified antibodies were better for sensitivity and for specificity than protein G-purified antibodies. The cross-reactivity of the purified antibodies seemed to be affected by immunogen structure and showed somewhat different patterns according to the immunoaffinity ligand utilized. These data show that the antibody purification method as well as choice of coating tracer and immunogen is essential for the sensitivity and specificity of EIA; the optimum condition for assay should be discovered using various methods and combinations.

• 대한핵의학회지
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• 제35권4호
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• pp.258-267
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• 2001

Purpose/Methods: Repeated administration of methamphetamine (METH) produces high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. The effect of MK-801, a noncompetitive N-methyl-D-aspartate receptor antagonist, on METH-induced changes in DA transporter (DAT) and DA release evoked by an acute METH challenge was evaluated in rodent striatum uslng $[^3H]$]WIN 38,428 ex vivo auto-radiography and in vivo microdialysis. Results: Four injections of METH (10 mg/kg, i.p.), each given 2 h apart, produced 71% decrease in DAT levels in mouse striatum 3 d after administration. Pretreatment with MK-801 (2.5 mg/kg, i.p.) 15 min before each of the four METH injections protected completely against striatal DAT depletions. Four injections of MK-801 alone did not significantly change striatal DAT levels. Striatal DA release evoked by an acute METH challenge (4 mg/kg, i.p.) at 3 d after repeated administration of METH in rats was decreased but significant compared with controls, which was attenuated by repeated pretreatment with MK-801. Also, repeated injections of MK-801 alone attenuated acute METH-induced striatal DA release 3 d after administration. Conclusion: These results suggest that repeated administration of MK-801 may exert a preventive effect against METH-induced DA terminal injury through long-term attenuation of DA release induced by METH and other stimuli.

• Toxicological Research
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• 제12권1호
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• pp.69-79
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• 1996

Primary culture of cerebellar neuronal cells derived from 8-day old Long-Evans rats was used. Pure granule cells, astrocytes or mixed cells culture systems were prepared. These cells were differentiated and developed synaptic connections. And the astrocytes were identified by immunostaining with glial fibrillary acidic protein (GFAP). Methamphetamine (MAP), which acts on dopaminergic system and cadmium (Cd), a toxic heavy metal, were applied and biochemical assays and electrophysiological studies were performed. $LC_50$ values estimated by MTT assay of MAP and Cd were 3 mM and 2$\mu M$ respectively. Cells were treated with 1 mM or 2 mM MAP and 1$\mu M$ $CdCl_2$ for 48 hour, and the incubation media were analyzed for the content of released LDH. MAP (2 mM) and Cd significantly increased the LDH release. Cell viability was decreased in both groups and some cytopathological changes like cell swelling or vacuolization were seen. The cerebellar granule cells were used for measuring membrane currents using whole-cell clamp technique. Sodium and potassium currents were not affected by MAP neither Cd, but calcium current was significantly reduced by Cd but not affected by MAP. Therefore, in vitro neurotoxicity test system using neuronaI cells and astrocytes cultures were established and can be used in screening of potential neurotoxic chemicals.