Lack of a role for the D3 receptor in clozapine induction of c-Fos demonstrated in D3 dopamine receptor-deficient mice
Lack of a role for the D3 receptor in clozapine induction of c-Fos demonstrated in D3 dopamine receptor-deficient mice
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DOI：
10.1016/s0306-4522(98)00498-9
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发表时间：
1999-01-01
期刊：
影响因子：
3.3
通讯作者：
Gerfen, CR
中科院分区：
文献类型：
--
作者：
Carta, AR;Gerfen, CR
用原位杂交组织化学方法分析D-3多巴胺受体在氯氮平作用中的作用，以检测与野生型小鼠相比，D-3多巴胺受体缺失小鼠不同脑区即刻早期基因c-fos的诱导情况。氯氮平治疗(15和30 mg/kg，S.C.)结果表明，纹状体、伏隔和隔区c-fos信使RNA的诱导呈剂量依赖性，前额叶皮质的c-fos信使RNA的诱导没有明显增加。在缺乏D-3受体的小鼠(D-3-/-)和野生型(D-3+/+)小鼠之间，这些区域的诱导水平没有发现差异。为了确定纹状体和伏隔核中哪些类型的神经元显示氯氮平(30 mg/kg)诱导c-fos信使RNA，用放射性c-fos信使RNA探针和地高辛标记的脑啡肽信使RNA探针进行了双标记实验，后者用作含D-2神经元的标记。氯氮平诱导的c-fos在脑啡肽阳性的纹状体神经元中有20%，在脑啡肽阳性的伏隔核神经元中有15%，在脑啡肽阴性的D-1神经元中约有10%，在D-3+/+和D-3-/-小鼠中都有检测到。这些结果表明，氯氮平对c-fos信使RNA的诱导不依赖于纹状体或伏核中的D-3多巴胺受体亚型。
The role of the D-3 dopamine receptor in mediating the effects of clozapine was analysed using in situ hybridization histochemistry to measure the induction of the immediate early gene c-fos in different brain areas of mice lacking a functional D-3 dopamine receptor compared to wild type mice. Clozapine treatment (15 and 30 mg/kg, s.c.) resulted in a' dose-dependent pattern of induction of c-fos messenger RNA in the striatum, accumbens and septal area, with a non-significant increase in the prefrontal cortex. There was no difference detected in any of these areas in the level of induction between mice lacking the D-3 receptor (D-3-/-) and wild type (D-3+/+) To determine which types of neurons in the striatum and accumbens displayed clozapine (30 mg/kg) induction of c-fos messenger RNA, a double-labeling experiment was performed using a radioactive c-fos messenger RNA probe and a digoxigenin-labeled enkephalin messenger RNA probe, the latter used as a marker of D-2-containing neurons. Clozapine-induced c-fos was detected in 20% of enkephalin-positive striatal neurons and 15% of enkephalin-positive accumbens neurons, and in both areas in about 10% of enkephalin-negative, putative D-1 neurons, in both D-3+/+ and D-3-/- mice.These results demonstrate that clozapine induction of c-fos messenger RNA is not dependent on the D-3 dopamine receptor subtype in the striatum or nucleus accumbens.