AUTORADIOGRAPHIC LOCALIZATION OF COCAINE BINDING-SITES BY [H-3] CFT ([H-3]WIN 35,428) IN THE MONKEY BRAIN

被引:102
作者
CANFIELD, DR [1 ]
SPEALMAN, RD [1 ]
KAUFMAN, MJ [1 ]
MADRAS, BK [1 ]
机构
[1] HARVARD UNIV, SCH MED, NEW ENGLAND REG PRIMATE RES CTR, 1 PINE HILL DR, SOUTHBOROUGH, MA 01772 USA
关键词
Autoradiography; Caudate; CFT; Cocaine receptors; Dopamine uptake sites; Nucleus accumbens; Putamen;
D O I
10.1002/syn.890060211
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The cocaine analog[3H]2β‐carbomethoxy‐3β‐(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 μM) to mask the binding sites. High densities of [3H]CFT binding sites were detecte in the caudate nucleus, putamen, and nucleus accumbens. In all three regions, binding was markedly reduced by coincubatin 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 biding 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 for the drugs in tissue sections corresponded closely with their reproted IC50 values in monkey caudate‐putamen membranes (r =0.99, p <0.0001), 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 dopmaine‐rich brain regions implicated in the behavioral effects and abuse of cocaine. Copyright © 1990 Wiley‐Liss, Inc.
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页码:189 / 195
页数:7
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