• Title, Summary, Keyword: Cocaine

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Effects of prenatal cocaine exposure on the developing rat :Pharmacological and neurobehavioral studies

  • Park, Sun-Ju
    • Proceedings of the Korean Society of Applied Pharmacology
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    • pp.171-172
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    • 1996
  • Cocaine is a powerful reinforcer that has become a popular drug of abuse in man. CNS effects that are related to the abuse of cocaine include feeling of well-being and euphoria. Brain dopamine systems are thought to mediate reinforcement and it is often assumed that cocaine's inhibition of dopamine uptake is the mechanism underlying its reinforcing effects. With increase in cocaine use among general population in recent years, adverse effects of the drug have occurred in all social strata and age groups. Therefore, it has been recognized that the epidemic of cocaine abuse is a growing major concerning public health. One of the most troubling aspects of cocaine abuse is its use by pregnant women. Drug abuse during pregnancy puts two lives at risk. Cocaine produces toxic effects on the fetus at concerntrations that are apparently nontoxic to the mother. Not only does cocaine cross the placenta via diffusion and via rapid penetration to mucous membranes, due to its high lipid solubility, but cocaine can also be found in breast milk, the effects of the cocaine can persist long after the child is born. Although it is known that prenatal cocaine exposure is associated with developmental risk to the fetus ana newborn, few studies have been conducted to assess the mechanisms whereby either short-term or long-term administration of cocaine can exert its harmful effects on the mother or the child. Therefore, it was our great interest to investigate the pharmacological and neurobehavioral changes in offspring that are prenatally exposed to cocaine.

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Behavioral Effects of Mianserin on the Developmental Toxicity of Cocaine

  • Kang, Dong-Won;Kim, Dong-Goo
    • Toxicological Research
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    • v.12 no.2
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    • pp.171-179
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    • 1996
  • To investigate the involvement of $5-HT_{2A}/ 5-HT_{2C} receptors in the developmental toxicity of cocaine in rats, mianserin (2.5 mg/kg), a $5-HT_{2A}/5-HT_{2C}$ receptor antagonist, and/or cocaine HCl (45 mg/kg) were administered intraperitoneally (i.p.), during postnatal days (PND) 7-13. Behavioral assessments for the rat pups were done after 100 days of age by using the progressive ratio schedule of reinforcement (FR 1-FR 128, doubled everyday) and cocaine challenge (5, 15 or 30 mg/kg i.p.) upon established FR 32 behavior. Cocaine injected just prior to the FR 32 session suppressed the established FR 32 responding in a dose-dependent manner. The low dose of cocaine did not affect the FR 32 responding, while the high dose of cocaine suppressed it in all experimental groups. However, by the middle dose of cocaine, rats previously received water-cocaine in their early life showed a marked resistance to cocaine-induced behavioral suppression, and this resistance was not observed in rats received both mianserin and cocaine in their early life. These results suggest that $5-HT_{2A}/ 5-HT_{2C}$ receptors may have an important role for the persistently altered behavioral sensitivity to cocaine caused by exposure to cocaine during development.

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Effects of Ginseng Saponins on Cocaine-Induced Hyperactivity, Reverse Tolerance and Dopamine Receptor Super-sensitivity in Mice (코카인으로 유도된 행동과다, 역내성 및 Dopamine 수용체 초과민성에 미치는 인삼 Saponin의 효과)

  • 김학성;정주연
    • Journal of Ginseng Research
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    • v.19 no.2
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    • pp.101-107
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    • 1995
  • The present study was undertaken to examine the effects of ginseng saponins [ginseng total saponin (GTS), protopanaxadiol saponin (PD) and protopanaxatriol saponin (PT)] on the hyperactivity, reverse tolerance and dopamine receptor super-sensitivity induced by cocaine. A single treatment with cocaine produced hyperactivity. Repeated administration of cocaine developed reverse tolerance and dopamine receptor super-sensitivity was also developed in reverse tolerant mice which had received the same cocaine. The hyperactivity and the developments of reverse tolerance and dopamine receptor super-sensitivity by cocaine were inhibited by ginseng saponins. From these results, it is proposed that ginseng saponins may be useful for the prevention and therapy of the adverse actions of cocaine. In addition, the rank order of inhibitory potential was observed as PT>GTS>PD. Key words Cocaine, hyperactivity, reverse tolerance, dopamine receptor super-sensitivity, ginseng saponins.

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Effect of Hyeongbangdojeok-san on Acute Cocaine-induced Behavioral Effect and Immediate Early Gene Expression in Rats. (형방도적산(荊防導赤散)이 급성코카인 투여로 인해 유도된 흰쥐의 행동량과 c-Fos 발현에 미치는 영향)

  • Seo, Ji-Yong;Choi, Ae-Ryun;Koo, Deok-Mo
    • Journal of Sasang Constitutional Medicine
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    • v.22 no.4
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    • pp.65-76
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    • 2010
  • 1. Objectives The present study was designed to investigate the effect of Soyangin Hyeongbangdojeok-san(HBDJS) on acute cocaine-induced behavior effect and gene expression in the rat brain. 2. Methods Experimental animals were composed of saline(SAL), cocaine(COC), HBDJS + COC, HBDJS + SAL group. Rats received HBDJS(100, 200 mg/kg, p.o.) 1 h prior to cocaine hydrochloride(20 mg/kg, i.p.) treatment respectively. After cocaine injection, locomotor activity and rearing were measured in a rectangular container equipped with a video camera above the center of the floor for 60 min. In addiction, c-Fos expression in the rat brain was detected using immunohistochemistry 2 h after cocaine injection. And the effect of HBDJS on acute cocaine-induced pERK, pElk, pCREB upstream of c-Fos expression was detected using western blotting and immunohistochemistry 15 min after cocaine challenge. 3. Results The present results show that HBDJS at dose of 200 mg/kg attenuated cocaine-induced both locomotor activity and rearing. Also HBDJS at dose of 200 mg/kg significantly decreased c-Fos expression in the rat brain(nucleus accumebns and striatum). However HBDJS at dose of 200 mg/kg have no effect on cocaine-induced pERK, pCREB, pElK-1 expression. HBDJS is c-Fos expression through ERK-independent pathway. 4. Conclusions. These results suggest that HBDJS may be effective in suppressing the reinforcing effects of cocaine.

Effect Of Cocaine Administration on the Development of Mouse Embryos

  • Kim, Soo-Hee;Yang, Boo-Keun;Kim, Hyoung-Chun;Jhoo, Wang-Kee
    • Archives of Pharmacal Research
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    • v.17 no.4
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    • pp.209-212
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    • 1994
  • Mophological normal of unfertilized oocytes, which was collected 12-14 hours after human Chorionic Gonadotropin(jCG) injection, was not influenced by chronically adiministration of cocaine for 2 weeks in mice. Proportion of normal unfertilized oocytes in non-cocaine treated group (control), `0 mg/kg and 20 mg/kg cocaine treated group based on body weight with subcutaneous(s.c.) daily injection of cocaine for 2 weeks were 92.9%, 85.6% and 90.9%, respectively. There is no significant difference between control and cocaine treated groups. Two to 8 cell stage embryos collected 24-48 hours post hCG in control group were 66.7%, whereas, 10 mg/kg and 20 mg/kg groups treated with cocaine was 12.5% and 27.3% respectively. Although control and treated groups are significantly different (p<0.05) the developmental score of 2 to 8 cell stage embryos collected at 24-48 hours post HCG, there is no difference between 10 mg/kg and 20 mg/kg treated with cocaine groups. These results indicated that the normal embryos of the roups of cocaine administration were significantly amested when compared with that of control group. The proportion of 2 to 8 cell stage embryo reaching the blastocyst stage, which were cultured 48-52 hours with 5% $Co_2$ in air at $37^{\circ}C$, were 93.9% in control group and, 70.4% and 71.9% in each 10 mg/kg and to blastocyst in vitro culture was significantly limited embryos obtained from cocanized mice compared with those of control mice. These results suggest that episode of cocaine intoxication can cause impaiment of early embrygenesis in the mouse.

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Ritanserin, a 5HT2/1C Receptor Antagonist, Does Not Block Cocaine-Induced Behavioral Alterations and zif268 mRNA Expression in the Striatum of the Rats

  • Choe, Eun-Sang;Kim, Jong-Yeon
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.5
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    • pp.355-359
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    • 2000
  • Cocaine induces immediate early gene expression and behavioral changes by blocking dopamine transporters in the terminals of nigrostriatal neurons in the striatum. The pharmacological role of serotonin 2/1C (5HT2/1C) receptors in cocaine-induced expression of zif268 (NGFI-A, egr1 and Krox-24) mRNA, a member of the zinc finger, was investigated using quantitative in situ hybridization histochemistry in vivo. Behavioral alterations induced by cocaine were also monitored in relation with blockade of the receptors. Systemic injection of ritanserin (1 mg/kg, s.c.), a 5HT2/1C receptor antagonist, did not reverse behavioral alterations and zif268 mRNA gene expression induced by 15 mg/kg cocaine, i.p., in the dorsal and ventral striatum. These data indicate that ritanserin-sensitive 5HT2/1C receptors are not necessary for cocaine-induced behavioral alterations and zif268 mRNA gene expression in the striatum.

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Cocaine-induced Changes in Functional Connectivities between Simultaneously Recorded Single Neurons in the SI Cortex and the VPL Thalamus of Conscious Rats

  • Shin, Hyung-Cheul;Park, Hyoung-Jin;Oh, Yang-Seok;Chapin, John K.
    • The Korean journal of physiology & pharmacology
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    • v.27 no.1
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    • pp.79-91
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    • 1993
  • The present study was carried out to determine the effects of cocaine (0.25, 1.0, 10.0 mg/kg, i.p.) on the interactions between spontaneously active neurons within ensembles of simultaneously recorded neurons in the primary somatosensory cortex (Sl, n= 20) and the ventroposterolateral (VPL, n= 16) thalamic nucleus of awake rats. Spike triggered cross correlation histograms were constructed between pairs of simultaneously recorded neurons. Among 101 neuronal pairs analyzed, 22.7% showed correlations indicative of various functional connections among the cortical cells, two corticothalamic interactions and one thalamocortical excitatory interaction. There were also 15 cofiring activities among SI cortical cells. These functional connectivities appeared to be modulated (weakened, abolished, or strengthened) during the 5 to 30 min following cocaine injection. The effects of saline were tested as a control, but it did not appear to alter the functional connectivities. In general, cocaine-induced changes of the functional interactions were mainly due to the concomitant alterations of the uncorrelated background discharges. These results suggest that the biphasic effects of cocaine on the spontaneously established neural networks among the SI cortical and the VPL thalamic cells of conscious rat were mainly indirect. However, various changes of the functional interactions by different doses of cocaine appeared to be a possible neural network mechanism for the cocaine induced modulation of afferent somatosensory transmission.

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Markers in Morphine- and Cocaine-Addicted Animals

  • Hu, Zhenzhen;Park, Kwang-Soon;Han, Jin-Yi;Jang, Choon-Gon;Oh, Sei-Kwan;Kim, Hyoung-Chun;Yang, Chae-Ha;Kim, Eun-Jeong;Oh, Ki-Wan
    • Biomolecules & Therapeutics
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    • v.19 no.1
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    • pp.45-51
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    • 2011
  • These experiments were designed to use typical makers from behaviors and molecular basis in addicted animals of morphine and cocaine. Morphine has been widely abused with a high physical dependence liability. Morphine withdrawal activates the intracellular cAMP signaling pathway and further leads to changes in the expression of the cAMP response element binding protein (CREB), which may be important to the development and expression of morphine dependence. From these experiments, repeated morphine (10 mg/kg, twice per day for 7 days) developed physical dependence. Withdrawal signs were precipitated by naloxone and also increased the expression of the CREB. In addition, repeated exposure of cocaine (15 mg/kg) to mice develops locomotor sensitization and produced lasting behavioral sensitivity. Cocaine- and amphetamine-regulated transcript peptide (CART) peptide was up-regulated by repeated administration of cocaine in the striatum. Therefore, repeated morphine induced the development of physical dependence and increased pCREB. In addition, repeated cocaine induced locomotor sensitization and over-expressed CART peptide. In conclusion, the development of physical dependence and pCREB for morphine, and locomotor sensitization and CART peptide over-expression for cocaine would be useful markers to predict the abuse potential of opioid analgesics and pychostimulant drugs in animals, respectively.

Acute cocaine intoxication in a body packer

  • Park, Mee-Jung;Lim, Mi-Ae;Chung, Hee-Sun
    • Analytical Science and Technology
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    • v.19 no.1
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    • pp.103-106
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    • 2006
  • A 35-year-old Perubian who suffered from grand mal seizures died in the aircraft on his way from the United States to Hongkong via Incheon international airport of Korea. While performing the autopsy, 115 packs made with double layer of transparent film and black plastic bag containing cocaine were found in the ileum and large intestine. Among of them, 3 packs were ruptured. To determine the concentration of cocaine and its metabolites, blood, urine, bile, liver, spleen, heart, kidney, brain and gastric contents were taken and toxicological analysis was performed. Gas chromatography/mass spectrometry (GC/MS) following liquid-phase extraction using chloroform:isopropanol (=9:1) and derivatization with bis(trimethylsilyl)-trifluoroacetamide (contains 1% trimethylchlorosilane) was performed. High levels of cocaine, benzoylecgonine (BE) and ecgonine methylester (EME) were found in the postmortem blood (0.96, 3.09 and $5.59{\mu}g/mL$) and urine (32.85, 145.35 and $53.17{\mu}g/mL$), respectively. Cocaine and its metabolites were also detected in all other biological specimen.

Amino Acid Structure of Dopamine Transporter Responsible for Cocaine Binding (코카인 결합과 관련된 도파민 수송체의 아미노산 구조)

  • 장미윤;전대준;오동렬;이용성;이상훈
    • YAKHAK HOEJI
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    • v.43 no.6
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    • pp.743-750
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    • 1999
  • Human and bovine dopamine transporters (DAT) demonstrate discrete functional differences in the dopamine (DA) transport and cocaine binding. The functional analyses on the chimeras of human and bovine DAT have revealed that the region from the $133^{rd}{\;}to{\;}186^{th}$ residue(encompassing the $3^{rd}$ trans-membrane domain (TM) is responsible for the substrate transport and cocaine binding. The present studies have been done to find out the specific amino acid(s) which is essential for the binding of cocaine to DAT by interchanging the amino acids in that region between human and bovine DAT. When isoleucine, the $152^{nd}$ residue of chimera B3 (bovine DAT sequence) was transformed back to valine, the human DAT residue at the identical position, the cocaine binding was remarkably recovered to 98% of the human DAT values. In addition, the cocaine binding of the human DAT was decreased by 57% by substituting isoleucine for valine at position 152. When isoleucine at position 152 of the chimera B3 was converted to the other amino acids to provide an possible molecular basis for the functional role of the $152^{nd}$ residue, only the conversion to alanine among acids tested significantly the cocaine by 34%, but these effect were not as much as those by the conversion to valine. In conclusion, valine at position 152 is a crucial amino acid for the interaction of cocaine to the DAT.

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