Alpha-7 nicotinic acetylcholine receptor agonists selectively activate limbic regions of the rat forebrain: An effect similar to antipsychotics
✍ Scribed by Henrik H. Hansen; Daniel B. Timmermann; Dan Peters; Carrie Walters; M. Imad Damaj; Jens D. Mikkelsen
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 386 KB
- Volume
- 85
- Category
- Article
- ISSN
- 0360-4012
No coin nor oath required. For personal study only.
✦ Synopsis
It is considered that activation of nicotinic a 7 receptors (a 7 nAChR) is useful for the treatment of cognitive disturbances in schizophrenia and Alzheimer's disease. Recently, selective a 7 nAChR agonists have been discovered and are used to validate the a 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 a 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 a 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 a 7 nAChR antagonist methyllycaconitine. Also, SSR180711 displayed no c-Fos-inducing effect in a 7 nAChR knockout mice. In conclusion, these results show that selective pharmacologic stimulation of a 7 nAChR function results in activation of forebrain regions similar to conventional antipsychotics. V