AUTORADIOGRAPHIC LOCALIZATION OF COCAINE BINDING-SITES BY [H-3] CFT ([H-3]WIN 35,428) IN THE MONKEY BRAIN
AUTORADIOGRAPHIC LOCALIZATION OF COCAINE BINDING-SITES BY [H-3] CFT ([H-3]WIN 35,428) IN THE MONKEY BRAIN
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DOI：
10.1002/syn.890060211
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发表时间：
1990-01-01
期刊：
影响因子：
2.3
通讯作者：
MADRAS, BK
中科院分区：
文献类型：
--
作者：
CANFIELD, DR;SPEALMAN, RD;MADRAS, BK
可卡因类似物[3 H] 2 β-甲氧羰基-3 β-（4-氟苯基）托烷（[3 H]CFT或[3 H]WIN 35，428）以高亲和力和选择性与猴尾壳核中的可卡因受体结合。[3 H]CFT用于使用放射自显影技术绘制猴脑载玻片切片中可卡因结合位点的区域分布。将半冠状脑切片与[3 H]CFT（3 nM）单独孵育或在过量（-）-可卡因（30 μ M）存在下孵育以掩蔽结合位点。高密度的[3 H]CFT结合位点在尾状核，壳核和丘脑核。在所有三个区域中，通过与未标记的（-）-可卡因共孵育，结合显著降低，表明非特异性结合水平低。在所研究的水平，在皮质、丘脑、苍白球或白色物质束中观察到很少或没有结合。为了表征组织切片中[3 H]CFT的结合位点，使用固定浓度的[3 H]CFT（3 nM）和一系列浓度的（-）-可卡因、（+）-可卡因、CFT、Lu 19-005、GBR 12909、安非他酮和西酞普兰进行竞争实验。猴尾壳核膜中的IC 50值（r = 0.99，p < 0.001），表明两种制剂中的[3 H]CFT结合相似。这些发现支持了这样的观点，即由[3 H]CFT标记的可卡因受体主要位于与可卡因的行为效应和滥用有关的富含多巴胺的脑区。
The cocaine analog [3H]2.beta.-carbomethoxy-3.beta.-(4-fluorophenyl)tropane ([3H]CFT or [3H]WIN 35,428) binds with high affinity and selectivity to cocaine receptors in the monkey caudate-putamen. [3H]CFT was used to map the regional distribution of cocaine binding sites in slide-mounted sections of monkey brains using autoradiographic techniques. Hemicoronal brain sections were incubated with [3H]CFT (3 nM) alone or in the presence of excess (-)-cocaine (30 .mu.M) to mask the binding sites. High densities of [3H]CFT binding sites were detected in the caudata nucleus, putamen and nucleus accumbens. In all three regions, binding was markedly reduced by coincubation with unlabeled (-)-cocaine, indicating low levels of nonspecific binding. Little or no binding was observed in the cortex, thalamus, globus pallidus, or white matter tracts at the levels studied. In order to characterize binding sites for [3H]CFT in tissue sections, competition experiments were conducted using a fixed concentration of [3H]CFT (3 nM) and a range of concentrations of (-)-cocaine, (+)-cocaine, CFT, Lu 19-005, GBR 12909, bupropion, and citalopram. The IC50 values in monkey caudate-putamen membranes (r = 0.99, p < 0.001), suggesting that [3H]CFT binding is similar in the two preparations. These findings support the view that cocaine receptors labeled by [3H]CFT are localized predominantly in dopamine-rich brain regions implicated in the behavioral effects and abuse of cocaine.