Alpha-7 nicotinic acetylcholine receptor agonists selectively activate limbic regions of the rat forebrain: An effect similar to antipsychotics
Alpha-7 nicotinic acetylcholine receptor agonists selectively activate limbic regions of the rat forebrain: An effect similar to antipsychotics
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DOI：
10.1002/jnr.21293
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发表时间：
2007-06-01
影响因子：
4.2
通讯作者：
Mikkelsen, Jens D.
中科院分区：
文献类型：
--
作者：
Hansen, Henrik H.;Timmermann, Daniel B.;Mikkelsen, Jens D.
It is considered that activation of nicotinic alpha(7) receptors alpha(7) nAChR) is useful for the treatment of cognitive disturbances in schizophrenia and Alzheimer's disease. Recently, selective alpha(7) nAChR agonists have been discovered and are used to validate the alpha(7) nAChR as a drug target for the treatment of cognitive disturbances in schizophrenia. One important feature shared by all known antipsychotics is their capacity to induce expression of the neuronal immediate-early gene c-fos in the limbic forebrain. Using two novel and selective alpha(7) nAChR agonists, PNU-282987 and SSR180711, we investigated their ability to induce c-Fos expression in the limbic forebrain with particular emphasis on the same regions reported to be activated by antipsychotics. Both alpha 7 nAChR agonists increased c-Fos dose-dependently in the prefrontal cortex and the shell of nucleus accumbens, while leaving the core of nucleus accumbens and the dorsolateral striatum unaffected. The accumbal and cortical effect of SSR180711 was blocked completely by pre-administration of the alpha(7) nAChR antagonist methyllycaconitine. Also, SSR180711 displayed no c-Fos-inducing effect in alpha(7) nAChR knockout mice. In conclusion, these results show that selective pharmacologic stimulation of alpha(7) nAChR function results in activation of forebrain regions similar to conventional antipsychotics. (c) 2007 Wiley-Liss, Inc.
