5-hydroxytryptamine(1B) receptors modulate the effect of cocaine on c-fos expression: Converging evidence using 5-hydroxytryptamine(1B) knockout mice and the 5-hydroxytryptamine(1B/1D) antagonist GR127935
5-hydroxytryptamine(1B) receptors modulate the effect of cocaine on c-fos expression: Converging evidence using 5-hydroxytryptamine(1B) knockout mice and the 5-hydroxytryptamine(1B/1D) antagonist GR127935
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DOI：
10.1124/mol.51.5.755
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发表时间：
1997-05-01
影响因子：
3.6
通讯作者：
Hen, R
中科院分区：
文献类型：
--
作者：
Lucas, JJ;Segu, L;Hen, R
血清素能传递被认为可以调节可卡因的作用。然而，这种现象背后的特定受体和大脑结构尚未确定。为了测试 5-羟色胺 (1B) (5-HT1B) 受体的可能贡献，我们研究了可卡因在缺乏该受体的基因敲除小鼠中诱导立即早期基因 c-fos 的情况。 5-HT1B 基因敲除小鼠表现出可卡因对不同大脑结构（尤其是纹状体）c-fos 诱导的影响显着降低。此外，给野生型小鼠施用 5-HT1B 受体激动剂 RU24969 会导致纹状体诱导 c-fos 表达，其时间过程、细胞和解剖分布以及药理学与可卡因诱导的表达非常相似。在这里，我们还报道了 5-HT1D 受体拮抗剂 GR127935 在体内拮抗 5-HT1D 受体的能力。最后，当给予野生型小鼠时，GR127935 降低了可卡因引起的纹状体 c-fos 表达的增加。通过敲除小鼠和 5-HT1B/1D 拮抗剂获得的这些证据表明，可卡因在体内充当 5-HT1B 受体的间接激动剂，并证明 5-HT1B 受体的激活有助于可卡因引起的细胞反应。
Serotonergic transmission has been suggested to modulate the effects of cocaine. However, the specific receptors and brain structures underlying this phenomenon have not been identified, To test the possible contribution of the 5-hydroxytryptamine(1B) (5-HT1B) receptor, we studied the induction of the immediate-early gene c-fos elicited by cocaine in knockout mice lacking this receptor. 5-HT1B knockout mice display a markedly reduced effect of cocaine on c-fos induction in different brain structures, most notably in the striatum. In addition, the administration to wild-type mice of the 5-HT1B receptor agonist RU24969 results in a striatal induction of c-fos expression very similar to that induced by cocaine in its time course, cellular and anatomical distribution, and pharmacology. Here, we also report the ability of a 5-HT1D receptor antagonist, GR127935, to antagonize 5-HT1D receptors in vivo. Finally, when administered to wild-type mice, GR127935 reduces the increase in striatal c-fos expression elicited by cocaine, These converging lines of evidence obtained with the knockout mice and 5-HT1B/1D antagonist indicate that cocaine acts as an indirect agonist of 5-HT1B receptors in vivo and demonstrate that activation of 5-HT1B receptors contributes to the cellular responses elicited by cocaine.