• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 제4회 추계심포지움
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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.

• Toxicological Research
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• 제12권2호
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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.

• Journal of Ginseng Research
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• 제19권2호
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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.

• 사상체질의학회지
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• 제22권4호
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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.

• 약학회지
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• 제43권6호
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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.

• Archives of Pharmacal Research
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• 제17권4호
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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.

• The Korean Journal of Physiology
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• 제27권1호
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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.

• Korean Journal of Acupuncture
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• 제19권1호
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• pp.25-33
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• 2002

Substantial evidence suggests that behavioral and reinforcing effects of cocaine can be mediated by the mesolimbic dopaminergic system. Injections of cocaine can produce one of the immediate-early gene, c-fos expression in the brain and behavioral activation. Acupuncture as a therapeutic intervention is widely used for the treatment of many mental disorders such as drugs of abuse. In order to investigate whether acupuncture has an influence on cocaine-induced reinforcing and behavioral effects, we examined the effect of acupuncture on cocaine-induced locomotor activity and c-Fos expression in the nucleus accumbens and the striatum using Fos-like-immunoreactivity(FLI). Male SD rats received acupuncture for 1 min after injection of cocaine hydrochloride(1 mg/kg, i.v.). The employed acupuncture point, Shenmen$(HT_7)$, has been clinically used to treat mental and psychosomatic disorders. Injections of cocaine produced a marked increase in locomotor activity and FLI in the nucleus accumbens and the striatum. Acupuncture at $HT_7$, but not at control points($PC_6,\;TE_4$ or tail), significantly attenuated cocaine-induced increase in locomotor activity and Fos-like immunoreactivity. These results demonstrated that reduction in locomotor activity by acupuncture may be reflected by reduction of postsynaptic neuronal activity in the nucleus accumbens and the striatum. Our results suggest that acupuncture may have a therapeutic effect on cocaine addiction.

• 분석과학
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• 제19권1호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제19권2호
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• pp.89-97
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• 2015

The aim of this study was to investigate the involvement of dopaminergic receptors (DR) in behavioral sensitization, as measured by locomotor activity, and the over-expression of cocaine- and amphetamine-regulated transcript (CART) peptides after repeated administration of cocaine in mice. Repeated administrations of cocaine induced behavioral sensitization and CART over-expression in mice. The levels of striatal CART mRNA were significantly increased on the $3^{rd}$ day. CART peptides were over-expressed on the $5^{th}$ day in the striata of behaviorally sensitized mice. A higher proportion of $CART^+$ cells in the cocaine-treated mice were present in the nucleus accumbens (NAc) shell than in the dorsolateral (DL) part of caudate putamen (CP). The concomitant administration of both $D_1R$ and $D_2R$ antagonists, SCH 23390 ($D_1R$ selective) and raclopride ($D_2R$ selective), blocked cocaine induced-behavioral sensitization, CART over-expression, and cyclic adenosine 5'-monophosphate (cAMP)/ protein kinase A (PKA)/phospho-cAMP response element-binding protein (pCREB) signal pathways. SCH 23390 more predominantly inhibited the locomotor activity, CART over-expression, pCREB and PKA activity than raclopride. Cocaine induced-behavioral sensitization was also attenuated in the both $D_1R$ and $D_2R$ knockout (KO) mice, respectively. CART over-expression and activated cAMP/PKA/pCREB signal pathways were inhibited in the $D_1R$-KO mice, but not in the $D_2R$-KO mice. It is suggested that behavioral sensitization, CART over-expression and activated cAMP/PKA/pCREB signal pathways induced by repeated administration of cocaine could be more predominantly mediated by $D_1R$.