title: Effects of repeated treatment with a delta opioid receptor agonist KNT-127 on hyperemotionality in olfactory-bulbectomized rats.
abstract: We previously demonstrated that a single treatment of a non-peptidic delta opioid receptor agonist, KNT-127, has an antidepressant-like effect in rodents in the forced swim test. Here we evaluated the effect of repeated administration of the potential antidepressant KNT-127 in an olfactory-bulbectomized (OBX) rat model. Male Wistar rats (8-12 weeks old) underwent olfactory bulbectomy. From 14days after surgery each was weighed and administered either KNT-127 (3mgkg-1/day), the selective serotonin reuptake inhibitor (SSRI) fluoxetine (10mgkg-1/day), or vehicle, daily for 14 days. Hyperemotionality was measured on days 3, 5, 7, 10, and 14. Repeated administration of KNT-127 significantly decreased total and individual hyperemotionality scores (attack, startle, struggle and fight) over the entire period. Conversely, fluoxetine did not show any significant effect on days 3, 5, 7, or 14 but significantly reduced the total score on day 10. The inhibitory effects of KNT-127 were greater than those of fluoxetine. The KNT-127 and control groups both gained weight, while the fluoxetine group lost weight. Our results suggest that KNT-127 is a potential lead compound for antidepressant therapy, with high efficacy, a relatively rapid onset of therapeutic effect, and without the possible adverse effects of weight loss caused by SSRIs.
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8553, Japan.
authors.forename: Leo
authors.initials: L
authors.lastname: Gotoh
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8553, Japan. Electronic address: asaito@ncnp.go.jp.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Saitoh
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8553, Japan.
authors.forename: Misa
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University, Tokyo 108-8641, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujii
authors.affiliation: International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagase
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8553, Japan.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001835:Body Weight / Q000187:drug effects; D003863:Depression / Q000517:prevention & control*; D004195:Disease Models, Animal; D004644:Emotions / Q000187:drug effects; D005473:Fluoxetine; D008297:Male; D009019:Morphinans / Q000008:administration & dosage*; D009830:Olfactory Bulb / Q000601:surgery; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000819:agonists*
chemical_list: D000928:Antidepressive Agents; C555233:KNT 127; D009019:Morphinans; D017465:Receptors, Opioid, delta; D005473:Fluoxetine
keywords: Animal model; Antidepressant; Delta opioid; Depression; KNT-127; Olfactory bulbectomy