• 생물정신의학
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• 제2권1호
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• pp.63-69
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• 1995

흰쥐에 항정신병약물인 haloperidol과 sulpiride를 장기간 투여한 뒤 줄무늬체와 후결절조직에서의 DA 수용체 의 변동에 대해 조사하였다. 이와 함께 apomorphine 투여에 따른 상동행동점수도 평가하였다. 흰쥐에 haloperidol(0.5mg/kg/day) 이나 sulpiride(40mg/kg/day)를 4주간 투여하고, 3일간의 약물 배설기간을 거친 후에 apomorphine(0.5mg/kg)을 투여하여 상동행동점수를 평가하였다. Haloperidol을 투여한 군에서는 대조군이나 sulpiride를 투여한 군에 비하여 상동행동에 대한 접수가 높게 나타났고, sulpiride를 투여한 군에서는 대조군과 유사한 정도의 상동행동을 나타내었다. 한편 줄무늬체 조직의 [$^3H$]spiperone의 결합에 대한 포화실험에서는 대조군에 비해 haloperidol이나 sulpiride를 투여한 군에서 최대결합치가 유의하게 증가되었다. 해리상수는 sulpiride투여시 줄무늬체에서 유의하게 감소되어 있었다. Sulpiride를 투여했을때 haloperidol 투여 시와 마찬가지의 DA수용체의 증식이 일어나지만, sulpiride 투여군에서만 상통행동 접수가 낮은 것으로 볼 때, 뇌의 DA계에서 sulpiride가 haloperidol과는 다르게 작용한다는 것을 간접적으로 시사하고 있다. 후결절에서는 sulpiride와 haloperidol을 투여한 양군에서 모두 최대결합치가 현저하게 증가되어 있었다. 또한 해라상수도 양군의 후결절에서 유의하게 증가되었다. 더욱이, 대조군은 후결절에서의 해리상수가 37.5pM, 줄무늬체에서는 86.2pM로 나타나, 후결절에서 줄무늬체에서보다 친화도가 두배 이상 높게 측정되었다. 위의 결과로 미루어 볼 때 sulpiride는 후결절에서 DA수용체의 증식을 유도할 뿐만 아니라 높은 친화력을 가진 몇몇 DA수용체 아형과도 상호작용을 한다는 것을 나타낸다. 또한 대조군에서 줄무늬체와 후결절에서의 친화도가 다른 점은, [$^3H$]spiperone에 반응한 DA수용체 아형은 줄무늬체와 후결절에서 각기 다르다는 점을 시사하고 있다.

• 한국동물학회지
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• 제34권4호
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• pp.491-499
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• 1991

The present experiment was carried out 1) to study the developmental topography of GnRH neuronal system and 2) to characterize the cellular localization of GnRH neurons in the prenatal brain development of the rat. At embryonic day (I) 14.5, immunoreactive cell bodies of GnRH were first seen in the nasal septum and in the ganglion terminate located in the ventral protion of the caudal olfactory bulb. Two days later (E 16.5), GnRH-containing neurons were observed at the level of olfactory tubercle and diagonal band of Broca, which is the first appearance in the intracerebral region. From 118.5, the topographic pattern of immunoreactive GnRH perikarya was similar to that of adult rats. The present data suggest that GnRH neurons were originated from the nasal septum and gradually extended to the hvpothalamic regions with increasing fetal age.

• 생물정신의학
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• 제3권2호
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• pp.240-244
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• 1996

흰쥐에 항정신병약물인 haloperidol을 장기간 투여한 뒤 줄무늬체와 후결절 조직에서의 DA $D_2$양 수용체의 변동에 대해 조사하였다. 약물투여군 4군에게 haloperidol을 각기 0.05, 0.15, 0.5, 1.5mg/kg/day이 되게끔 4주간 투여하였다. DA수용체의 변동은 [$^3H$]spiperone을 이용한 결합반응법을 통해 알아 보았다. 정상대조군에 비해 4주 동안 haloperidol을 투여받은 군 모두에서 줄무늬체에서의 DA 수용체의 최대 결합치가 증가한 것으로 나타났다. 기존의 연구에서 사용한 용량보다 대단히 낮은 0.05mg/kg/day을 투여받은 군 역시 유의한 증가를 보여 낮은 용량의 haloperidol이 DA계에 영향을 미치는 것을 알 수 있었다. 후결절조직의 최대결합치는 haloperidol투여군 모두에서 증가한 경향을 볼 수 있었으나 정상대조군에 비해 1.5mg/kg/day투여군에서 유의한 증가를 볼 수 있었다. 본 실혐의 결과로 미루어 낮은 용량의 haloperidol을 장기간 투여했을 때 뇌내 DA계에 수용체증식이 나타나며 항정신병 효과의 발현과도 관련성이 시사된다. 이러한 결과는 최근 거론되고 있는 항정신병약물의 저용량투여를 간접적으로 지지하는 것으로 생각되며 DA계의 연동을 알리는 다른 생물학적 지표와의 관련성을 살피면 흥미로운 결과를 얻을 것으로 기대된다.

• 생명과학회지
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• 제11권1호
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• pp.1-7
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• 2001

The caffeine intake cause a local or wide ranges of convulsion and it is associated with release of dopamine (DA) receptors into the brain striatum. However, the effect of caffeine addiction on expression of DA receptors gene in the rat caudate-putamen (CPu), nucleus accumbens (NAc), and olfactory tubercle (OTu) has not been elucidated. In this study, we examined the influence of caffeine addiction on DA D $_1$and D$_2$receptor mRNAs after the treatment of caffeine for four weeks. Using the specific antisense ribo-probes for DA D$_1$and D$_2$receptor cDNAs, in situ hybridization was performed on the CPu, NAc, and OTu of the adult male Sprague Dawely rats. In caffeine-treated group, DA D$_1$and D$_2$receptor mRNAs were highly increased in CPu, NAc, and OTu. The expression density of DA D$_1$receptor mRNAs were 2.52${\pm}$1.40 (CPu), 2.78${\pm}$1.69 (NAc), and 3.91${\pm}$1.28 (OTu) in control group and 7.76${\pm}$2.09 (CPu), 4.2 ${\pm}$1.85 (NAc), and 8.21${\pm}$1.72 (OTu) in caffeine-treated group. The expression density of DA D$_2$receptor mRNA was 2.32${\pm}$1.52 (CPu), 2.63${\pm}$2.11 (NAc), and 3.61${\pm}$1.43 (OTu) in control group, and 6.41${\pm}$1.82 (CPu), 6.89${\pm}$1.32 (NAc), and 6.82${\pm}$1.18 (OTu) in caffeine-treated group. DA D$_1$receptor mRNA was higher expressed than DA D$_2$ receptor mRNA in CPu and NAc. These results suggest that caffeine reacts as a upregulator of the expression of DA D$_1$and D$_2$receptor mRNA among the neurotransmitters.

• The Korean Journal of Physiology and Pharmacology
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• 제1권1호
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• pp.1-12
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• 1997

As it has been reported that the depolarization induced acetylcholine (ACh) release is modulated by activation of presynaptic $A_1$ adenosine heteroreceptor and various evidence suggest that indicate the $A_2$ adenosine receptor is present in the striatum, this study was undertaken to delineate the role of adenosine receptors on the striatal ACh release. Slices from the rat striatum were equilibrated with $[^3H]$choline and then the release amount of the labelled product, $[^3H]$ACh, which was evoked by electrical stimulation (rectangular pulses, 3 Hz, 2 ms, 24 mA, $5\;Vcm^{-1}$, 2 min), was measured, and the influence of various agents on the evoked tritium outflow was investigated. And also, quantitative receptor autoradiography and drug-receptor binding assay were performed in order to confirm the presence and characteristics of $A_1$ and $A_2$ adenosine receptors in the rat striatum. Adenosine $(10{sim}100\;{mu}M)$ and $N^6$-cyclopentyladenosine (CPA, $1{sim}100\;{mu}M)$ decreased the $[^3H]$ACh release in a dose-dependent manner without changing the basal rate of release in the rat striatum. The reducing effects of ACh release by adenosine and CPA were abolished by 8-cyclopentyl-1,3-dipropy-Ixanthine (DPCPX, 2 ${mu}M$), a selective $A_1$, adenosine receptor antagonist, treatment. The effect of adenosine was potentiated markedly by 3,7-dimethyl-1-propargylxanthine (DMPX, 10 ${mu}M$), a specific $A_2$ adenosine receptor antagonist. 2-P-(2-carboxyethyl)phenethylamimo-5'-N- ethylcarboxamidoadenosine hydrochloride (CGS-21680C), in concentrations ranging from 0.01 to 10 ${mu}M$, a recently introduced potent $A_2$ adenosine receptor agonist, increased the $[^3H]$ACh release in a dose related fashion without changing the basal rate of release. These effects were completely abolished by DMPX $(10\;{mu}M)$. In autoradiograrhy experiments, $[^3H]$2-chloro-$N^6$-cyclopentyladenosine ($[^3H]$ CCPA) bindings were highly localized in the hippocampus and the cerebral cortex. Additionally, lower levels of binding were found in the striatum. However, $[^3H]$CGS-21680C bindings were highly localized in the striatal region with the greatest density of binding found in the caudate nucleus and putamen. Lower levels of binding were also found in the nucleus accumbens and olfactory tubercle. In drug-receptor binding assay, binding of $[^3H]$ CCPA to $A_1$ adenosine receptors of rat striatal membranes was inhibited by CPA ($K_i$ = 1.6 nM) and N-ethylcarboxamidoadenosine (NECA, $K_i$ = 12.9 nM), but not by CGS-21680C ($K_i$ = 2609.2 nM) and DMPX ($K_i$ = 19,386 nM). In contrast, $[^3H]$CGS-21680C binding to $A_2$ denosine receptors was inhibited by CGS-21680C ($K_i$ = 47.6 nM) and NECA ($K_i$ = 44.9 nM), but not by CPA ($K_i$ = 2099.2 nM) and DPCPX ($K_i$ = 19,207 nM). The results presented here suggest that both types of $A_1$ and $A_2$ adenosine heteroreceptors exist and play an important role in ACh release in the rat striatal cholinergic neurons.