Comparison of the kappa-opioid receptor antagonist DIPPA in tests of anxiety-like behavior between Wistar Kyoto and Sprague Dawley rats
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.
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.
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.
WKY rats displayed greater amounts of anxiety-like behavior compared to SD rats. DIPPA produced anxiolytic-like effects in both tests in both strains.
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.
KeywordsWistar Kyoto rat Anxiety Kappa-opioid receptor Defensive burying Novelty-induced hypophagia
The authors are grateful for the valuable technical assistance of Matthew Young. This research was supported by funds from AstraZeneca and the National Institute of Mental Health (T32 MH14652).
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