Köster A, Montkowski A, Schulz S, Stübe E M, Knaudt K, Jenck F, Moreau J L, Nothacker H P, Civelli O, Reinscheid R K
F. Hoffmann-La Roche AG, Pharma Division, CNS Research, CH-4070 Basel, Switzerland.
Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10444-9. doi: 10.1073/pnas.96.18.10444.
The neuropeptide orphanin FQ (also known as nociceptin; OFQ/N) has been implicated in modulating stress-related behavior. OFQ/N was demonstrated to reverse stress-induced analgesia and possess anxiolytic-like activity after central administration. To further study physiological functions of OFQ/N, we have generated OFQ/N-deficient mice by targeted disruption of the OFQ/N gene. Homozygous mice display increased anxiety-like behavior when exposed to a novel and threatening environment. OFQ/N-null mice show elevated basal pain threshold but develop normal stress-induced analgesia. Interestingly, these mice show impaired adaptation to repeated stress when compared with wild-type mice, whereas their performance in spatial learning remained unaffected. Basal and poststress plasma corticosterone levels were found to be elevated in OFQ/N-deficient animals. Thus, OFQ/N appears to be crucially involved in the neurobiological regulation of stress-coping behavior and fear.
神经肽孤啡肽FQ（也称为痛敏肽；OFQ/N）被认为参与调节应激相关行为。已证明中枢给予OFQ/N可逆转应激诱导的镇痛作用并具有抗焦虑样活性。为了进一步研究OFQ/N的生理功能，我们通过靶向破坏OFQ/N基因产生了OFQ/N基因缺陷小鼠。纯合子小鼠在暴露于新的威胁环境时表现出焦虑样行为增加。OFQ/N基因敲除小鼠的基础痛阈升高，但应激诱导的镇痛作用正常。有趣的是，与野生型小鼠相比，这些小鼠在适应反复应激方面受损，而它们在空间学习方面的表现不受影响。发现OFQ/N缺陷动物的基础和应激后血浆皮质酮水平升高。因此，OFQ/N似乎在应激应对行为和恐惧的神经生物学调节中起关键作用。
