title: Targeted disruption of the orphanin FQ/nociceptin gene increases stress susceptibility and impairs stress adaptation in mice.
abstract: 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.
authors.affiliation: F. Hoffmann-La Roche AG, Pharma Division, CNS Research, CH-4070 Basel, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Köster
authors.forename: A
authors.initials: A
authors.lastname: Montkowski
authors.forename: S
authors.initials: S
authors.lastname: Schulz
authors.forename: E M
authors.initials: EM
authors.lastname: Stübe
authors.forename: K
authors.initials: K
authors.lastname: Knaudt
authors.forename: F
authors.initials: F
authors.lastname: Jenck
authors.forename: J L
authors.initials: JL
authors.lastname: Moreau
authors.forename: H P
authors.initials: HP
authors.lastname: Nothacker
authors.forename: O
authors.initials: O
authors.lastname: Civelli
authors.forename: R K
authors.initials: RK
authors.lastname: Reinscheid
mesh_terms: D000698:Analgesia; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D018782:Maze Learning; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D018847:Opioid Peptides / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D010465:Perception; D011957:Receptors, Opioid / Q000502:physiology; D013028:Space Perception; D013315:Stress, Psychological / Q000235:genetics* / Q000503:physiopathology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D003345:Corticosterone; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722287:Oprl1 protein, mouse