Gregory V Carr1, Irwin Lucki. 1. Department of Psychiatry, University of Pennsylvania, 125 South 31st Street, Room 2204, Philadelphia, PA, USA.
Abstract
RATIONALE: Recent evidence suggests a role for the dynorphin/kappa-opioid receptor (KOR) system in the expression of stress-induced behaviors. Wistar Kyoto (WKY) rats exhibit increased depression-like and anxiety-like responses in behavioral tests compared to other strains and may be a model of comorbid depression and anxiety characterized by increased activity within the dynorphin/KOR system. Though KOR antagonists produce antidepressant-like effects in WKY rats, their effects in tests of anxiety-like behavior have not been examined in the WKY strain. OBJECTIVE: The aim of the current study was to investigate the effects of the KOR antagonist 2-(3,4-dichlorophenyl)-N-methyl-N-[(1S)-1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl]acetamide hydrochloride (DIPPA) on the behavior of WKY rats and Sprague Dawley (SD) rats in tests of anxiety-like behavior. METHODS: The novelty-induced hypophagia and defensive burying tests were used to measure anxiety-like behavior in WKY and SD rats and determine the effects of DIPPA on anxiety-like behavior in both strains. RESULTS: WKY rats displayed greater amounts of anxiety-like behavior compared to SD rats. DIPPA produced anxiolytic-like effects in both tests in both strains. CONCLUSIONS: WKY rats display more anxiety-like behavior at baseline compared to SD rats, and DIPPA produced anxiolytic-like effects in both WKY and SD rats. These findings support previous research suggesting that KOR antagonists possess anxiolytic-like properties and may potentially represent a novel class of treatments for mood disorders.
RATIONALE: Recent evidence suggests a role for the dynorphin/kappa-opioid receptor (KOR) system in the expression of stress-induced behaviors. Wistar Kyoto (WKY) rats exhibit increased depression-like and anxiety-like responses in behavioral tests compared to other strains and may be a model of comorbid depression and anxiety characterized by increased activity within the dynorphin/KOR system. Though KOR antagonists produce antidepressant-like effects in WKY rats, their effects in tests of anxiety-like behavior have not been examined in the WKY strain. OBJECTIVE: The aim of the current study was to investigate the effects of the KOR antagonist 2-(3,4-dichlorophenyl)-N-methyl-N-[(1S)-1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl]acetamide hydrochloride (DIPPA) on the behavior of WKY rats and Sprague Dawley (SD) rats in tests of anxiety-like behavior. METHODS: The novelty-induced hypophagia and defensive burying tests were used to measure anxiety-like behavior in WKY and SD rats and determine the effects of DIPPA on anxiety-like behavior in both strains. RESULTS: WKY rats displayed greater amounts of anxiety-like behavior compared to SD rats. DIPPA produced anxiolytic-like effects in both tests in both strains. CONCLUSIONS: WKY rats display more anxiety-like behavior at baseline compared to SD rats, and DIPPA produced anxiolytic-like effects in both WKY and SD rats. These findings support previous research suggesting that KOR antagonists possess anxiolytic-like properties and may potentially represent a novel class of treatments for mood disorders.
Authors: Nasim Ahmadiyeh; Gary A Churchill; Kazuhiro Shimomura; Leah C Solberg; Joseph S Takahashi; Eva E Redei Journal: Mamm Genome Date: 2003-11 Impact factor: 2.957
Authors: Leah C Solberg; Amber E Baum; Nasim Ahmadiyeh; Kazuhiro Shimomura; Renhua Li; Fred W Turek; Gary A Churchill; Joseph S Takahashi; Eva E Redei Journal: Mamm Genome Date: 2004-08 Impact factor: 2.957
Authors: Ashlee Van't Veer; Anita J Bechtholt; Sara Onvani; David Potter; Yujun Wang; Lee-Yuan Liu-Chen; Günther Schütz; Elena H Chartoff; Uwe Rudolph; Bruce M Cohen; William A Carlezon Journal: Neuropsychopharmacology Date: 2013-02-27 Impact factor: 7.853