Egashira Nobuaki, Harada Satoko, Okuno Ryoko, Matsushita Michihiko, Nishimura Ryoji, Mishima Kenichi, Iwasaki Katsunori, Orito Kensuke, Fujiwara Michihiro
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka and Department of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, Japan.
Eur J Pharmacol. 2007 Jun 1;563(1-3):149-54. doi: 10.1016/j.ejphar.2007.02.019. Epub 2007 Feb 17.
In the present study, we examined the involvement of the sigma1 receptor in the inhibitory effect of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine, compared with that of paroxetine, on marble-burying behavior, which is an animal model of obsessive-compulsive disorder. Sigma1 receptor agonists (+)-SKF 10047 and PRE-084 significantly inhibited marble-burying behavior. Sigma receptor antagonist BD 1047 and selective sigma1 receptor antagonist BD 1063 significantly attenuated the inhibition of marble-burying behavior by fluvoxamine. In contrast, selective sigma2 receptor antagonist SM-21 failed to affect the inhibition of marble-burying behavior by fluvoxamine. On the other hand, BD 1047 and BD 1063 had no effect on the inhibition of marble-burying behavior by paroxetine. These observations show that activation of the sigma1 receptor is a necessary component in the inhibitory effect of fluvoxamine on marble-burying behavior, and that the mechanism of its action is clearly different from that of paroxetine.
在本研究中，我们研究了σ1受体在选择性5-羟色胺再摄取抑制剂（SSRI）氟伏沙明与帕罗西汀相比对大理石埋藏行为的抑制作用中的参与情况，大理石埋藏行为是强迫症的一种动物模型。σ1受体激动剂（+）-SKF 10047和PRE-084显著抑制大理石埋藏行为。σ受体拮抗剂BD 1047和选择性σ1受体拮抗剂BD 1063显著减弱了氟伏沙明对大理石埋藏行为的抑制作用。相反，选择性σ2受体拮抗剂SM-21未能影响氟伏沙明对大理石埋藏行为的抑制作用。另一方面，BD 1047和BD 1063对帕罗西汀对大理石埋藏行为的抑制作用没有影响。这些观察结果表明，σ1受体的激活是氟伏沙明对大理石埋藏行为抑制作用的必要组成部分，并且其作用机制与帕罗西汀明显不同。
