title: DOR(2)-selective but not DOR(1)-selective antagonist abolishes anxiolytic-like effects of the δ opioid receptor agonist KNT-127.
abstract: Recently, we reported that the δ opioid receptor (DOR) agonist KNT-127 produces anxiolytic-like effects in behaving rats. Here, we report on the roles of DOR subtypes ( DOR(1) and DOR(2)) play in mediating KNT-127-induced anxiolytic-like effects. Pretreatment with the DOR(2)-selective antagonist naltriben (NTB; 0.05mg/kg, s.c.) completely abolished KNT-127 (3.0mg/kg, s.c.)-induced anxiolytic-like effects in rats performing the elevated plus-maze task. By contrast, the DOR(1)-selective antagonist 7-benzylidenenaltrexone (BNTX; 0.5mg/kg, s.c.) produced no effect at a dose that completely blocked the antinociceptive effects of KNT-127. These findings were also supported by results from a light/dark test and open-field test. We clearly demonstrated that the DOR(2)-selective antagonist, but not the DOR(1)-selective antagonist, abolishes the anxiolytic-like effects of the DOR agonist KNT-127, suggesting different roles of these DOR subtypes in anxiety. We propose that DOR(2)-selective agonists would be good candidates for future development of anxiolytic drugs.
authors: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashimachi, Kodaira, Tokyo 187-8553, Japan; Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
authors: Azusa
authors: A
authors: Sugiyama
authors: International Institute for Integrative Sleep Medicine, University of Tsukuba, Ibaraki 305-8577, Japan.
authors: Hiroshi
authors: H
authors: Nagase
authors: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
authors: Jun-Ichiro
authors: J
authors: Oka
authors: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashimachi, Kodaira, Tokyo 187-8553, Japan.
authors: Mitsuhiko
authors: M
authors: Yamada
authors: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashimachi, Kodaira, Tokyo 187-8553, Japan. Electronic address: asaito@ncnp.go.jp.
authors: Akiyoshi
authors: A
authors: Saitoh
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy; D001597:Benzylidene Compounds / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D005557:Formaldehyde; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009019:Morphinans / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009483:Neuropsychological Tests; D059225:Nociception / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*
chemical_list: D014151:Anti-Anxiety Agents; D001597:Benzylidene Compounds; C000593231:DOR2 protein, rat; C555233:KNT 127; D009019:Morphinans; D009292:Narcotic Antagonists; C000593230:Oprd1 protein, rat; D017465:Receptors, Opioid, delta; C068868:naltrindole benzofuran; C077358:7-benzylidenenaltrexone; D005557:Formaldehyde; D009271:Naltrexone
keywords: Analgesia; Animal models; Antidepressants; Anxiolytics; Inflammatory pain