Uchiyama Hidemori, Yamaguchi Taku, Toda Akihisa, Hiranita Takato, Watanabe Shigenori, Eyanagi Reiko
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Eur J Pharmacol. 2008 Aug 20;590(1-3):185-9. doi: 10.1016/j.ejphar.2008.05.031. Epub 2008 May 29.
We investigated the mechanism underlying the anxiolytic actions of the neuropeptide nociceptin/orphanin FQ (N/OFQ) with an elevated plus-maze test. In mice, intracerebroventricular (i.c.v.) infusions of N/OFQ (0.1 and 0.32 nmol) led to an increase in time spent in the open arms (anxiolytic-like effects). A non-peptidyl N/OFQ receptor (NOP) antagonist, J-113397(1-{(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl}-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one), (1.0 and 3.2 mg/kg, s.c.) blocked the increase induced by N/OFQ. On the other hand, a benzodiazepine receptor antagonist, flumazenil, (10 mg/kg, i.p.) and a GABAA receptor antagonist, (+)-bicuculline, (5.6 mg/kg, i.p.) also inhibited the increase induced by N/OFQ. In rats, microinfusions of N/OFQ (10 and 32 pmol) into the amygdala led to an increase in time spent in the open arms. However, intracranial infusions of N/OFQ (10-100 pmol) into the dorsal hippocampus did not affect the time spent in the open arms. These findings suggest that the anxiolytic-like effects of N/OFQ may be related to the GABA/benzodiazepine system in the amygdala.
我们通过高架十字迷宫试验研究了神经肽孤啡肽/痛敏肽（N/OFQ）抗焦虑作用的潜在机制。在小鼠中，脑室内（i.c.v.）注射N/OFQ（0.1和0.32 nmol）导致在开放臂停留时间增加（类抗焦虑作用）。一种非肽类N/OFQ受体（NOP）拮抗剂J-113397（1-{(3R,4R)-1-环辛基甲基-3-羟甲基-4-哌啶基}-3-乙基-1,3-二氢-2H-苯并咪唑-2-酮）（1.0和3.2 mg/kg，皮下注射）可阻断N/OFQ诱导的增加。另一方面，苯二氮䓬受体拮抗剂氟马西尼（10 mg/kg，腹腔注射）和GABAA受体拮抗剂荷包牡丹碱（5.6 mg/kg，腹腔注射）也抑制N/OFQ诱导的增加。在大鼠中，向杏仁核微量注射N/OFQ（10和32 pmol）导致在开放臂停留时间增加。然而，向背侧海马颅内注射N/OFQ（10 - 100 pmol）不影响在开放臂停留的时间。这些发现表明，N/OFQ的类抗焦虑作用可能与杏仁核中的GABA/苯二氮䓬系统有关。
