Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Basic Clin Pharmacol Toxicol. 2009 Nov;105(5):333-8. doi: 10.1111/j.1742-7843.2009.00449.x. Epub 2009 Jul 15.
The effects of unilateral intra-ventral hippocampus injection of URB597, a fatty acid amid hydrolase inhibitor, and AM251, a selective CB(1) receptor antagonist, on anxiety-related behaviours using elevated plus-maze test of anxiety were evaluated in the present study. Possible involvement of GABAergic system in those effects of URB597 was also evaluated. Injection of URB597 at the doses of 0.01, 0.1 and 1 microg/rat showed significant anxiogenic-like effects at 0.1 and 1 microg/rat. However, intra-ventral hippocampus injection of AM251 at the doses of 0.001, 0.01 and 0.1 microg/rat did not produce any significant effect in the elevated plus-maze. The ineffective doses of selective GABA(A) receptor antagonist, bicuculline (2 microg/rat) and selective GABA(B) receptor antagonist, phaclofen (1 microg/rat) on anxiety-related behaviours were also injected with URB597 (0.1 microg/rat). The present data showed that neither bicuculline nor phaclofen affected the anxiogenic-like effects of URB597. The results showed that injection of URB597 into the ventral hippocampus may be anxiogenic and GABAergic system may not be involved in its anxiogenic-like effects.
本研究采用高架十字迷宫焦虑测试，评估了脂肪酸酰胺水解酶抑制剂 URB597 和选择性 CB1 受体拮抗剂 AM251 单侧脑室注射对焦虑相关行为的影响。还评估了 URB597 作用中 GABA 能系统的可能参与。URB597 以 0.01、0.1 和 1μg/大鼠的剂量注射显示出 0.1 和 1μg/大鼠时明显的类焦虑样作用。然而，AM251 以 0.001、0.01 和 0.1μg/大鼠的脑室注射剂量在高架十字迷宫中没有产生任何显著影响。还将选择性 GABA(A)受体拮抗剂荷包牡丹碱（2μg/大鼠）和选择性 GABA(B)受体拮抗剂 phaclofen（1μg/大鼠）的无效剂量与 URB597（0.1μg/大鼠）一起注射。目前的数据表明，荷包牡丹碱或 phaclofen均不会影响 URB597 的类焦虑样作用。结果表明，URB597 脑室注射可能具有焦虑作用，而 GABA 能系统可能不参与其类焦虑样作用。
