• Title/Summary/Keyword: new cocaine

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Immunohistochemical detection of GluA1 subunit of AMPA receptor in the rat nucleus accumbens following cocaine exposure

  • Cai, Wen Ting;Han, Joonyeup;Kim, Wha Young;Kim, Jeong-Hoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.1
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    • pp.79-85
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    • 2021
  • α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are differentially regulated in the nucleus accumbens (NAcc) of the brain after cocaine exposure. However, these results are supported only by biochemical and electrophysiological methods, but have not been validated with immunohistochemistry. To overcome the restriction of antigen loss on the postsynaptic target molecules that occurs during perfusion-fixation, we adopted an immersion-fixation method that enabled us to immunohistochemically quantify the expression levels of the AMPA receptor GluA1 subunit in the NAcc. Interestingly, compared to saline exposure, cocaine significantly increased the immunofluorescence intensity of GluA1 in two sub-regions, the core and the shell, of the NAcc on withdrawal day 21 following cocaine exposure, which led to locomotor sensitization. Increases in GluA1 intensity were observed in both the extra-post synaptic density (PSD) and PSD areas in the two sub-regions of the NAcc. These results clearly indicate that AMPA receptor plasticity, as exemplified by GluA1, in the NAcc can be visually detected by immunohistochemistry and confocal imaging. These results expand our understanding of the molecular changes occurring in neuronal synapses by adding a new form of analysis to conventional biochemical and electrophysiological methods.

Transgenic Mice Overexpressing Cocaine-Amphetamine Regulated Transcript in the Brain and Spinal Cord (뇌와 척수에서 Cocaine-Amphetamine Regulated Transcript를 과발현하는 형질전환 생쥐)

  • Choi, S.H.;Lee, J.W.;Park, H.D.;Jahng, J.W.;Chung, K.S.;Lee, H.T.
    • Korean Journal of Animal Reproduction
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    • v.25 no.4
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    • pp.389-397
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    • 2001
  • Cocaine-amphetamine regulated transcript (CART), a satiety factor regulated by leptin, is associated with food intake and motor behavior. In knock out studies, Leu34Phe mutation of human CART gene resulted in obese phenotype but mice carrying a targeted deletion of the CART gene exhibited no dramatic increase of body weight on normal fat diet. To establish a new transgenic mouse model for determining the function of CART on feeding behavior in vivo, we constructed the fusion gene, CART gene under the control of neurofilament light chain promoter, which regulates gene expression at the stage of neuronal differentiation. Transgenic mice were generated by microinjection method and screened by PCR and Southern blot analyses. In these transgenic mice, overexpression of CART was detected by in situ hybridization in spinal cords and brains at 13.5 days post-coitum embryos. At six weeks of age, RT-PCR analysis showed that exogenous CART mRNA was expressed strongly in brains and spinal cords, but not much in other tissues. Our results suggest that these transgenic mice provide a new model to investigate the function of CART gene in neuronal network associated with feeding behavior.

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Application of the $^{32}$P-Postlabelling Technique : A Study on Detection of DNA Adduct Induced by Azo Dyes rind Flavonoid Compounds ($^{32}$P-Postlabelling 방법의 응용 : Azo색소 및 Flavonoid화합물에 의해 유도되는 DNA Adduct의 겸출에 관한 연구)

  • 김재현;박창원;박정식;홍연탁;김효정;이주한;이헌수;이동권
    • Biomolecules & Therapeutics
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    • v.1 no.1
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    • pp.58-64
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    • 1993
  • DNA addicts induced by putative chemical related to carcinogenesis were detected and determined by $^{32}$P-Postlabelling assay after exposure of 4 compounds comprising two auto dyes (amaranth, new coccine) and two flavonoid compounds (rutin, quercetin) to ICR mouse. DNA was isolated from mouse liver and digested enzymatically to deoxyribonucleoside 3'-monophosphate. The postincubation of DNA digests with nuclease Pl before $^{32}$P-labelling enhanced the technique's sensitivity. Nuclease Pl cleaves deoxyribonucleoside 3'-mono-phosphates of normal nucleotides to deoxyrihonucleosides which do not serve as substrates for polynucleotide kinase, while most of addicts were found to be totally or partially resistant to the 3'-dephosphorylating action of nuclease Pl. The adducted deoxyribonucleoside 3'-monophosphate was converted to 5'-$^{32}$P-labelled deoxynucleoside 3',5'-bisphosphate by T4 polynucleotide kinase. The nucleotides were separated by anion-exchange thin layer chromatography(TLC) on polyethyleneimine cellulose by 4-dimensional or 2-dimensional TLC then detected by autoradiography. The results show that DNA addicts were detected in liver DNA of ICR mouse after administration of amaranth and quercetin by 2-dimensional and/or 4-dimensional TLC.

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Invertebrate Models Used for Characterization of Drug Dependence and Development of Anti-Drug Dependent Agents

  • Chang Hyun-Sook;Kim Ha-Won;Lee Dong-Hee
    • Biomolecules & Therapeutics
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    • v.14 no.1
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    • pp.1-10
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    • 2006
  • Drug dependence deals a heavy socioeconomic burden to the society. For adolescents, the damage from drug dependence is greater than adults considering their higher susceptibility to drug effect and increasing chance for violence leading to criminal punishment process. Habitual drug use depends on genetic and environmental factors and the complex interactions between the two. Mammalian model systems have been useful in understanding the neurochemical and cellular impacts of abused drugs on specific regions of the brain, and in identifying the molecular targets of drugs. More elucidation is required whether biological effects of drugs actually cause the habitual dependence at the cellular level. Although there is much insight available on the nature of drug abuse problems, none of the systems designed to help drug dependent individuals is efficient in screening functional ingredients of the drug, and thus resulting in the failure of helping drug dependent individuals recover from drug dependence. Alternative model systems draw the attention of researchers, such as the invertebrate model systems of nematodes (Caenorhabditis elegans) and fruit flies (Drosophila melanogaster). These models should provide new insight into the mechanisms leading to the behavior of drug users (even functional studies analyzing molecular mechanism), and screening useful components to help remove drug dependence among drug users. The relatively simple anatomy and gene expression of the invertebrate model systems should enable researchers to coordinate current knowledge on drug abuse. Furthermore, the invertebrate model systems should facilitate advance in experiments on the susceptibility of specific genetic backgrounds and the interaction between genetic factors to drug dependence.

Distribution of Abused Drugs in 275 Alcohol-positive Blood Samples of Korean Driver (음주운전자 275명 혈액 중 마약류 및 남용약물의 분석)

  • Choi, Hye-Young;Lee, Ju-Seon;Choi, Sang-Kil;Kim, Eun-Mi;Kim, Jae-Kyun;Kim, Young-Woon;Lim, Mi-Ae;Chung, Hee-Sun
    • YAKHAK HOEJI
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    • v.52 no.2
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    • pp.137-146
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    • 2008
  • Even though driving under the influence of drug (DUID) is a worldwide problem, we, Korea has no regulation system yet except for alcohol, and there are little cases reported related to DUID. In order to investigate the type of abused drugs for drivers in Korea, we tried to analyze controlled and non-controlled drugs in alcohol-positive blood samples. 275 whole bloods, which were positive for alcohol on the roadside test, were collected from the police for two months ($Nov.{\sim}Dec.$ 2006). The analytical strategy was constituted of three steps: First, alcohol in blood samples were confirmed and quantified by gas chromatography. Second, controlled drugs were screened by $Evidence_{investigator}\;^{TM}$ (Randox, U.K.) as preliminary test. It was based on immunoassay by biochip array analyzer. Nine groups of drug abuse were screened: amphetamines, methamphetamines, cannabis, cocaine, opiates, barbiturates, methadone, benzodiazepines I (oxazepam) & II (lorazepam). Finally, confirmation of these drugs was performed by GC-MS. Blood samples were extracted by solid-phase extraction by $RapidTrace^{TM}$ (Zymark, U.S.A.). After trimethylsilyl (TMS) derivatization, eluates were analyzed to GC-MS. Total 49 drugs were investigated in this study including controlled drugs, antidepressants, 1st generation antihistamines, dextromethorphan, nalbuphine, ketamine, etc. For rapid detection, we developed the automated identification system. It was made up a new software, "DrugMan", modified Chemstation data analysis menu and newly developed macro modules. A series of peak selection, identification and reporting of the results were performed automatically by this system. Concentrations of alcohol in 275 blood samples were ranged from 0.011 to 0.249% (average, 0.119%). Among 149 blood samples, just six samples (4.0%) were showed positive results to the immunoassay: one methamphetamine and five benzodiazepines group I. By GC-MS confirmation, only benzodiazepines were detected and methamphetamine was not detected from immunoassay positive blood sample. Besides these drugs, 5 chlorpheniramines, dextromethorphan, diazepam, doxylamine, ibuprofen, lidocaine and topiramate were also detected in whole bloods by GC-MS. Conclusively, the frequency of drug abuse for Korean drivers was relatively low. There was none case which illegal drug was detected. However these results were limited to alcohol positive blood samples, so it is necessary to analyze more samples including alcohol negative blood.

Trend and Future of Virtual Reality for Addiction Treatment of Substance Use Disorders: A Systematic Review (가상현실을 활용한 중독치료의 동향과 전망을 위한 체계적 문헌고찰)

  • Amista, Narcie Faith;Kim, Jinsoo Jason;Kim, Nami
    • Journal of Digital Contents Society
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    • v.18 no.8
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    • pp.1551-1560
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    • 2017
  • The aim of this review is to analyze the trend of using Virtual Reality (VR) in addiction treatment by categorizing the types of addictions and methods of Virtual Reality Therapy (VRT) for substance use disorders. VR has been utilized as a new paradigm for treating various mental and psychological problems. In recent years, a number of researches have been done to demonstrate the effectiveness of VRT for addiction treatment, specifically substance use disorders. In order to comprehend the tendency of these researches, the current study performed a systematic review of published book and journal articles using the following bibliographical databases: ScienceDirect, MEDLINE, ProQuest, and Embase. Forty-five (45) articles were retrieved; out of these researches, nicotine/smoking has garnered the highest number of studies (73%, n=33); alcohol (18%, n=8); cannabis/marijuana (2%, n=1); and other drugs such as heroin, cocaine and methamphetamine (7%, n=3). This paper analyzed the results of those studies, found some limitations as well as strengths, and made suggestions for further research on VRT for addiction treatment.