Mamiya T, Noda Y, Nishi M, Takeshima H, Nabeshima T
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466, Japan.
Brain Res. 1998 Feb 9;783(2):236-40. doi: 10.1016/s0006-8993(97)01406-6.
We isolated genes for the opioid receptor homologue MOR-C, namely nociceptin receptor (designated alternatively as orphanin FQ receptor) and generated nociceptin receptor-knockout mice. Previously, we have reported that the nociceptin system appears to participate in the regulation of the auditory system. However, the behavior of the nociceptin receptor-knockout mice has yet to be fully characterized. In the present study, we investigated changes in several behavioral performances in mice which lack nociceptin receptor. Nociceptive thresholds of nociceptin receptor-knockout mice were unchanged in the hot-plate and electric foot-shock tests as well as tail-flick and acetic-acid-induced writhing tests compared to those of wild-type mice. The nociceptin receptor-knockout mice did not show any behavioral changes in the elevated plus-maze task. Surprisingly, in the water-finding test, the nociceptin receptor-knockout mice showed an enhanced retention of spatial attention (latent learning) compared to wild-type mice. In a biochemical study, dopamine content in the frontal cortex was lower in nociceptin receptor-knockout mice than wild-type mice. These results suggest that nociceptin receptor plays an important role in spatial attention by regulating the dopaminergic system in the brain.
我们分离出了阿片受体同源物MOR-C的基因，即孤啡肽受体（也称为孤啡肽FQ受体），并培育出了孤啡肽受体基因敲除小鼠。此前，我们曾报道孤啡肽系统似乎参与了听觉系统的调节。然而，孤啡肽受体基因敲除小鼠的行为尚未得到充分表征。在本研究中，我们调查了缺乏孤啡肽受体的小鼠在几种行为表现上的变化。与野生型小鼠相比，在热板试验、电足电击试验以及甩尾试验和醋酸诱导扭体试验中，孤啡肽受体基因敲除小鼠的伤害性感受阈值没有变化。在高架十字迷宫试验中，孤啡肽受体基因敲除小鼠没有表现出任何行为变化。令人惊讶的是，在水迷宫试验中，与野生型小鼠相比，孤啡肽受体基因敲除小鼠在空间注意力（潜在学习）的保持方面有所增强。在一项生化研究中，孤啡肽受体基因敲除小鼠额叶皮质中的多巴胺含量低于野生型小鼠。这些结果表明，孤啡肽受体通过调节大脑中的多巴胺能系统在空间注意力方面发挥重要作用。
