title: Further characterization of the prototypical nociceptin/orphanin FQ peptide receptor agonist Ro 64-6198 in rodent models of conflict anxiety and despair.
abstract: BACKGROUND
  Ro 64-6198, the prototypical non-peptide nociceptin/orphanin FQ peptide (NOP) receptor agonist, has potent anxiolytic-like effects in several preclinical models and species. However the effects of Ro 64-6198 on distinctive anxiety-provoking conditions related to unconditioned conflict behavior as well as its role in despair-like behavior remain to be addressed.
  
  
  OBJECTIVE
  Here we examined the effects of Ro 64-6198 on unconditioned conflict anxiety using stimuli with different salience and on regulation of autonomic reactivity and compared these to the effects of benzodiazepine receptor agonists. We also addressed the potential effects of Ro 64-6198 on despair-like behavior.
  
  
  METHODS
  Ro 64-6198 (0.1 to 10 mg/kg i.p.) and either diazepam or chlordiazepoxide were tested in the Vogel conflict punished drinking test (VCT) in Sprague Dawley rats, in the social approach-avoidance (SAA) test in Lewis rats, in the novelty-induced hypophagia (NIH) in C57BL/6J mice, and in stress-induced hyperthermia in NMRI mice, as well as in the forced swim test (FST) in Sprague Dawley rats and the tail suspension test (TST) in C57BL/6J mice.
  
  
  RESULTS
  Ro 64-6198 (0.3 to 3 mg/kg) dose-dependently produced anxiolytic-like effects in the VCT, SAA, NIH, and SIH, similar to benzodiazepine receptor agonists. Ro 64-6198 did not alter immobility time in the FST and TST.
  
  
  CONCLUSIONS
  Ro 64-6198 produced marked anxiolytic-like effects in response to a variety of mild to strong anxiogenic stimuli, whereas it did not facilitate depression-related behaviors. This data extend previous literature suggesting that NOP receptors are a viable target for the treatment of anxiety disorders.
authors.affiliation: CNS Research, CNS Discovery, pRED, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, CH-4070 Basel, Switzerland.
authors.forename: Celia
authors.initials: C
authors.lastname: Goeldner
authors.forename: Will
authors.initials: W
authors.lastname: Spooren
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wichmann
authors.forename: Eric P
authors.initials: EP
authors.lastname: Prinssen
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects; D002707:Chlordiazepoxide / Q000494:pharmacology; D003220:Conflict, Psychological; D003863:Depression / Q000188:drug therapy*; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists*; D013141:Spiro Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D013315:Stress, Psychological / Q000188:drug therapy; D000094942:Nociceptin Receptor
chemical_list: D014151:Anti-Anxiety Agents; D007093:Imidazoles; D011957:Receptors, Opioid; C408068:Ro 64-6198; D013141:Spiro Compounds; D002707:Chlordiazepoxide; D003975:Diazepam; D000094942:Nociceptin Receptor