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标题：Inhibitory Effects of Osemozotan, a Serotonin 1A-Receptor Agonist, on Methamphetamine-Induced c-Fos Expression in Prefrontal Cortical Neurons
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作者：Rie Tsuchida ; Masahiro Kubo ; Norihito Shintani 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2009
卷号：32
期号：4
页码：728-731
DOI：10.1248/bpb.32.728
出版社：The Pharmaceutical Society of Japan
摘要：Psychostimulants induce hyperlocomotion in normal subjects, although, they are effective in producing a calming effect in hyperactive subjects. This paradoxical effect has been related to changes in serotonin (5-HT) neurotransmission in hyperactive dopamine transporter-knockout mice. In addition, we observed that hyperlocomotion in mice lacking pituitary adenylate cyclase-activating polypeptide was attenuated by amphetamine dependent on 5-HT_1A receptor signaling and that amphetamine, when co-administered with a 5-HT_1A agonist, produced a calming effect in wild-type mice. Here, in an attempt to address how 5-HT_1A receptor signaling exerts the calming action of psychostimulants, we examined c-Fos expression in several brain regions after administration of methamphetamine and osemozotan, a selective 5-HT_1A receptor agonist. The number of c-Fos-positive cells was increased in the medial prefrontal cortex, striatum and nucleus accumbens in methamphetamine (3 mg/kg body weight)-injected mice. Osemozotan (1 mg/kg) significantly reduced the methamphetamine-induced c-Fos expression in the medial prefrontal cortex and striatum, but not in the nucleus accumbens. This osemozotan action was completely blocked by the 5-HT_1A receptor antagonist WAY-100635 (1 mg/kg). As the prefrontal cortex is considered to be involved in the beneficial actions of psychostimulant medications for attention-deficit/hyperactivity disorder, the present result showing 5-HT_1A-mediated inhibition of corticostriatal activity may partly be related to this psychostimulant action.
关键词：serotonin 5-HT1A receptor;medial prefrontal cortex;psychostimulant;c-Fos;osemozotan;striatum