Augmentation of Regional Cerebral Blood Flow Response by Repeated Administration of Methamphetamine in Rat

Woo Seong Jang,Jeong Gee Kim,Ji Do Park,Hyun Kyoung Choi,Hee Sun Chung,Su Yeon Ko,이원석 대한정신약물학회 2003 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.1 No.1

challenge test in rats subjected to repeated administration of methamphetamine, and to investigate the mechanism (s) underlying the changes in rCBF response in relation to the dopaminergic receptors and cyclic AMP. Male Sprague-Dawley rats received daily injections of methamphetamine (0.3 mg/kg, i.p.) for 10 days and were then allowed a 4-day drugfree period. Naive and methamphetamine-pretreated rats were challenged with topical application of methamphetamine on the surface of the parietal cortex through a cranial window. The changes in rCBF were measured by laser-Doppler flowmetry. Acute topical application of methamphetamine concentration-dependently increased rCBF with little effect on mean arterial blood pressure. The methamphetamine-induced increases in rCBF were significantly blocked by SCH23390, a D1-like receptor antagonist, but not by sulpiride, a D2-like receptor antagonist. Repeated administration of methamphetamine induced progressive augmentation of the rCBF in response to the methamphetamine challenge. Repeated administration of methamphetamine in combination with SKF38393, a D1-like receptor agonist, as well as with SCH23390 significantly attenuated the augmentation of the rCBF response to methamphetamine. The augmentation of the rCBF response was markedly inhibited by pretreatment with both 2’,3’-dideoxyadenosine, a specific adenylyl cyclase inhibitor, and by Rp-cAMPS, a protein kinase A inhibitor. These results suggest that repeated methamphetamine administration induces an augmentation of the rCBF in response to methamphetamine challenge, and D1-like receptor-mediated cyclic AMP plays a critical role in the development of methamphetamine-induced rCBF response augmentation. challenge test in rats subjected to repeated administration of methamphetamine, and to investigate the mechanism (s) underlying the changes in rCBF response in relation to the dopaminergic receptors and cyclic AMP. Male Sprague-Dawley rats received daily injections of methamphetamine (0.3 mg/kg, i.p.) for 10 days and were then allowed a 4-day drugfree period. Naive and methamphetamine-pretreated rats were challenged with topical application of methamphetamine on the surface of the parietal cortex through a cranial window. The changes in rCBF were measured by laser-Doppler flowmetry. Acute topical application of methamphetamine concentration-dependently increased rCBF with little effect on mean arterial blood pressure. The methamphetamine-induced increases in rCBF were significantly blocked by SCH23390, a D1-like receptor antagonist, but not by sulpiride, a D2-like receptor antagonist. Repeated administration of methamphetamine induced progressive augmentation of the rCBF in response to the methamphetamine challenge. Repeated administration of methamphetamine in combination with SKF38393, a D1-like receptor agonist, as well as with SCH23390 significantly attenuated the augmentation of the rCBF response to methamphetamine. The augmentation of the rCBF response was markedly inhibited by pretreatment with both 2’,3’-dideoxyadenosine, a specific adenylyl cyclase inhibitor, and by Rp-cAMPS, a protein kinase A inhibitor. These results suggest that repeated methamphetamine administration induces an augmentation of the rCBF in response to methamphetamine challenge, and D1-like receptor-mediated cyclic AMP plays a critical role in the development of methamphetamine-induced rCBF response augmentation.

필로폰중독 선별검사표 개발에 관한 예비연구(Ⅰ)

김원(Won Kim),김경빈(Kyung-Bin Kim),오동열(Dong-Yul Oh) 한국중독정신의학회 1998 중독정신의학 Vol.2 No.2

This is a preliminary study to develop a self-reporting scale that can tell methamphetamine addictor from the simple user of methamphetamine. If once a patient gets dependent upon methamphetamine, recovery from the addiction becomes a very difficult process, and medical support will be needed. Therefore the fundamental solution for methamphetamine problem is to give opportunities of participation in recovery programs to the already dependant addictors among the drug users who are considered to be criminals in general. In order to do this, the discrimination of methamphetamine addictors from simple methamphetamine users must be preceded. This is the reason why we need to develop Methamphetamine Addiction Screening Test (MAAST). As a preparation for the development of MAAST, we have made a survey on prisoners in three penitentiaries in Korea in order to have subjects who have experienced using mehtamphetamine. 373 items were offered to be answered to 265 prisoners related to methamphetamine, and their answers were analyzed. They were classified into Methamphetamine Dependence Group (N=199) and Methamphetamine Non-dependence Group (N=66) according to DSM-IV criteria, and we have chosen 72 items of questions that tells the differences between the two groups quite well through chi-square test. Among these items, correlated ones were divided into 13 categories, and the coefficiency of the items and the internal consistency of these categories were ensured by Cronbach s α coefficients. The items we got from this study will be used as candidate questionnaire for the final settlement of MAAST through the next study.

Acupuncture inhibits psychostimulant effect of methamphetamine via rostromedial tegmental area

( Min Young Yim ) 대구한의대학교 제한동의학술원 2021 제한동의학술원논문집 Vol.19 No.1

Background : Methamphetamine is a representative psychostimulant that has been abused world wide. The reinforcing effects of methamphetamine is known to stronger than any other abused drug due to its neuronal action to the dopanine release in the nucleus accumbens (NAc) synapse. In the previous studies, acupuncture has shown to suppress spontaneous intake as well as reinstatement of addiction in a intravenous methamphetamine self-administration rat model. In addition, acupuncture inhibited the increase of brain temperature by methamphetamine. Based on, the present study examined if acupuncture could suppress methamphetamine-induced increase of brain temperature and a possible neuronal mechanism was also investigated. Materials and Methods : Male Sprague-Dawley rats (250-280 g at begining) were acclimated to the experimental envronment for at lease 3 days. For the measurement of the changes of brain temperature by acute administration of methamphetamine, animals were anesthetized using intraperitoneal injection of sodium pentobarbital (50 mg/kg) and placed at a stereotaxic apparatus. An access hole was made by drill through the skull for the NAc and a thermocouple needle microprobe was carefully placed at the destination. A second thermocouple probe was inserted into the rectum for the measurement of body temperature. Temperature was recorded for 60 minutes using a digital thermometer and a computerized data acquisition system. Temperature measurement was conducted at room temperature and during body warming by a heating pad set at 36.5℃. After baseline recording during about 30 minutes, methamphetamine (0.5 mg/kg) was intraperitoneally administered and the recordings continued for another 30 minutes. For the electronic lesion, electrodes were inserted into the each target area of rostromedial tegmental area (RMTg), lateral habenula (LHb), prefrontal cortex (PFC), and central amygdala (CeA). Results : Acute administration of methamphetamine increased the temperature in the MAc of mesolimbic system. However acupuncture inhibited this increase of brain temperature when stimulated at HT7 (神門), but not at TE9 (四瀆). In addition, this inhibitory effect of acupuncture at HT7 disappeared when the RMTg was blocked by electronic lesion. Also, in the following examination, none of the electronic lesion in the LHb, PFC, nor CeA blocked HT7 effect. Conclusion : Acupuncture at HT7 inhibited the increase of brain temperature in the NAc by methamphetaine and this inhibition of acupuncture was blocked by the lesion of the RMTg. Results of the present study suggest that acupuncture at HT7 can be a useful therapy for the methamphetamine addiction.

메스암페타민 검사 양성 환자에 대한 임상적 고찰: 단일기관 연구

옥영빈,김진용,이경룡,홍대영,백광제,박상오,김종원,김신영,Ok, Young Bin,Kim, Jin Yong,Lee, Kyeong Ryong,Hong, Dae Young,Baek, Kwang Je,Park, Sang O,Kim, Jong Won,Kim, Sin Young 대한임상독성학회 2018 대한임상독성학회지 Vol.16 No.1

Purpose: Methamphetamine is an ongoing illegal drug problem worldwide, and its use in South Korea has spread over the last few years. In this study, a clinical review of patients who visited emergency medical centers with positive methamphetamine tests was conducted. Methods: Patients underwent methamphetamine screening based on physician suspicion over a period of 13 years. Their patient characteristics, clinical features, and drug administration properties were described. Results: A total of 297 patients were included, with 19 positive methamphetamine results. Patient age ranged from 21 to 84, with a mean of 37.52. Additionally, 13 were male and 6 were female. The mean BP, PR, RR were 131/82 mmHg, 94/min, 20/min. Saturation levels were all over 95%. Five patients had a psychiatric history. Patient showed varied symptoms ranging from mental changes to chest discomfort. In addition, seven showed abnormal electrocardiography findings and one showed elevated cardiac enzyme levels. Other laboratory results revealed no significantly abnormal results. Six patients also suffered from related trauma. The majority of patients consumed the methamphetamine orally, with unknown motivation at unknown locations. Most were transported by 119 and six patients co-ingested other drugs. Conclusion: Patients who showed positive results to a methamphetamine screening test in Korea visited the emergency medical center mostly by 119 and were unaware of or reluctant to reveal the fact that they had ingested methamphetamine. Emergency physicians should be more aware of the possibility that a patient may have consumed methamphetamine.

1980년대 한국의 마약소비와 확산

조석연(Cho, Seok-yeon) 역사실학회 2016 역사와실학 Vol.61 No.-

This article is a review of studies of the drug problem in the 1980s. In the 1980s, Korea methamphetamine problem was a serious social problem. Korea and Japan in the 1980s was interrupted by a joint drug trafficking. Therefore, the methamphetamine produced in Korea in the 1980s, has never been exported to Japan. And the methamphetamine produced in Korea were brought back to Korea. Meth addicts in the 1980s, Korea has increased every year. Methamphetamine has been introduced according to Seoul from Busan Gyeongnam and Gyeongbuk. Korea"s economy has grown significantly in the 1980s. Korea has hosted the Olympic Games in the Asian Games, in 1986 and 1988. Korea in the Asian Games and Olympics was recognized as a national event. And Korea has grown significantly entertainment industry in the 1980s. Methamphetamine addicts, Korea was increasing in the 1980s. It was because increasing the income and consumption of the people. The government has pointed to problems with methamphetamine ‘social evils". And the government tried to eradicate methamphetamine. The government has strengthened enforcement and penalties for drug users. But methamphetamine addicts has increased. Looking at the Methamphetamine problem and government policy in the 1980s can be found inconsistencies. It is a methamphetamine problem has been developed in a different direction and intention of the government at the time. Thus, the drug problem has been highlighted as the most important social issue in Korea in the 1980s. This article also examined the government"s recognition and response to the drug problem. The government has used the drug for social control in 1980s. Korea has continued to strengthen the enforcement and penalties for drugs. However, treatment and rehabilitation institutions for drug addiction had shortage. Therefore, the government was promoting a drug called ‘social evils" to the people. Drug addicts in Korea have been promoting the community as a "criminal" rather than "patients".

Protective Effects of Isoliquiritigenin Against Methamphetamine-Induced Neurotoxicity in Mice

Lee, Min Jung,Yang, Chae Ha,Jeon, Jae-Pil,Hwang, Meeyul The Japanese Pharmacological Society 2009 JOURNAL OF PHARMACOLOGICAL SCIENCES Vol.111 No.2

<P>Isoliquiritigenin (ISL) suppresses cocaine-induced extracellular dopamine levels and has a neuroprotective effect in cocaine-treated rat brain. Here, we examine the effect of ISL on methamphetamine-induced striatal neurotoxicity. Repeated injections of methamphetamine cause the loss of striatal dopamine transporter (DAT) and tyrosine hydroxylase (TH). Intraperitoneal injection of ISL prior to methamphetamine injection significantly prevented methamphetamine-induced reduction of DAT and TH. ISL also suppressed methamphetamine-induced activation of glial cells. Moreover, ISL impeded the expression of nitric oxide synthase and the activation of NF-κB through blockage of its phosphorylation. Our results suggest that ISL protects against methamphetamine-induced neurotoxicity by inhibition of NF-κB activation.</P>

Comparative analysis of urinary metabolites in methamphetamine self-administrated rats

Choi, Boyeon,Kim, Soo Phil,Jang, Choon-Gon,Yang, Chae Ha,Lee, Sooyeun The Korean Society of Analytical Science 2017 분석과학 Vol.30 No.3

Methamphetamine addiction is a critical issue due to the lack of effective pharmacotherapy and high potential for relapse. Nevertheless, there are no distinct biomarkers for diagnosis or prognosis for methamphetamine addiction. In the present study, a rat model for methamphetamine self-administration was established and alteration of urinary metabolites by methamphetamine addiction was investigated by the targeted metabolite analysis using mass spectrometry. Rat urine samples were collected at three time points (before and after addiction and after extinction) from the methamphetamine-addicted group as well as the age-matched control group. The collected samples were prepared using AbsoluteIDQ p180 kit and analyzed using flow injection analysis (FIA) - or high performance liquid chromatography (HPLC) - tandem mass spectrometry (MS/MS). The levels of lysine, acetylornithine and methioninesulfoxide were distinctively altered depending on the status of metheamphetamine addiction or extinction. In particular, the level of acetylornithine was reversely changed from addiction to extinction, for which further studies could be useful for biomarker discovery or mechanistic studies for methamphetamine addiction.

정신병적 증상의 동반 여부에 따른 메스암페타민 남용자들의 인격 특성 비교

이정현(Jeong-Hyeon Lee),권도훈(Do-Hoon Kwon),이병대(Byung-Dae Lee),김양태(Yang-Tae Kim),조수현(Soo-Hyun Joe),이영민(Young-Min Lee),문은수(Eun-Soo Moon),조성남(Sung-Nam Cho) 한국중독정신의학회 2010 중독정신의학 Vol.14 No.1

Objectives:This study aimed to investigate personality profile differences among methamphetamine abusers admitted to Bugok National Hospital according to the presence or absence of psychotic features. Participants & Methods:Participants were 37 hospitalized male patients who met the DSM-IV criteria for methamphetamine abuse or dependence. We evaluated their psychotic symptoms using the Brief Psychiatric Rating Scale (BPRS). To measure personality traits, we used the Temperament and Character Inventory (TCI) and the NEO Five Factor Inventory (NEO-FFI). We used the independent t-test to analyze differences in inventory profiles between participants with the sole diagnosis of Methamphetamine Dependence with, or without, psychotic symptoms. Results:Compared with their non-psychotic counterparts, methamphetamine users with psychotic features showed significantly higher Novelty-Seeking and, Harm Avoidance and lower Extraversion. Conclusion:This study suggests that differences in methamphetamine abusers’ personality profiles might suggest possible vulnerability to methamphetamine-induced psychotic features. Further trials, larger and well-designed, could more accurately define differences in personality profiles between methamphetamine users with psychotic features and without psycho-tic features.

Comparative analysis of urinary metabolites in methamphetamine self-administrated rats

최보연,이수연,김수필,장춘곤,양채하 한국분석과학회 2017 분석과학 Vol.30 No.3

Methamphetamine addiction is a critical issue due to the lack of effective pharmacotherapy and high potential for relapse. Nevertheless, there are no distinct biomarkers for diagnosis or prognosis for methamphetamine addiction. In the present study, a rat model for methamphetamine self-administration was established and alteration of urinary metabolites by methamphetamine addiction was investigated by the targeted metabolite analysis using mass spectrometry. Rat urine samples were collected at three time points (before and after addiction and after extinction) from the methamphetamine-addicted group as well as the age-matched control group. The collected samples were prepared using AbsoluteIDQ p180 kit and analyzed using flow injection analysis (FIA) - or high performance liquid chromatography (HPLC) - tandem mass spectrometry (MS/MS). The levels of lysine, acetylornithine and methioninesulfoxide were distinctively altered depending on the status of metheamphetamine addiction or extinction. In particular, the level of acetylornithine was reversely changed from addiction to extinction, for which further studies could be useful for biomarker discovery or mechanistic studies for methamphetamine addiction.

흰쥐의 급성 메스암페타민 투여에 대한 鍼의 효과

최성훈,이봉효,박인식,최난희,김광중,장은영,구세광,송익수,양재하 대한침구의학회 2009 대한침구의학회지 Vol.26 No.1

Objectives : The mesolimbic dopamine system is believed to play a major role in the reinforcing effect and behavioral hyperactivity of abused drugs including methamphetamine. In the present study, the effect of acupuncture on methamphetamine-induced locomotor activity and c-Fos expression in the striatum and nucleus accumbens of rats were examined. Methods : Male Sprague-Dawley rats received acupuncture at bilateral Yanggu(SI5) point for 30seconds immediately before the subcutaneous injection of saline or methamphetamine(0.5mg/kg). The total amount of locomotor activity for 90min were measured just before brain samples were taken for immunohistochemistry. Results : Results showed that acupuncture at the specific point SI5, but not control point (Kunlun, BL60) significantly reduced locomotor activity and c-Fos expression in the striatum and nucleus accumbens induced by acute administration of methamphetamine. Conclusions : These results suggest that acupuncture may be effective in suppressing the reinforcing effect of methamphetamine by regulating neuronal activity.