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Comparative Study
. 2010 Jun;210(2):295-302.
doi: 10.1007/s00213-010-1832-9. Epub 2010 Apr 6.

Comparison of the kappa-opioid receptor antagonist DIPPA in tests of anxiety-like behavior between Wistar Kyoto and Sprague Dawley rats

Gregory V Carr  1 , Irwin Lucki
Affiliations
Comparative Study

Comparison of the kappa-opioid receptor antagonist DIPPA in tests of anxiety-like behavior between Wistar Kyoto and Sprague Dawley rats

Gregory V Carr et al. Psychopharmacology (Berl). 2010 Jun.

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.

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Figures

Fig. 1
Fig. 1
Effects of DIPPA in the NIH novel cage test. a Latency to approach food. b Amount of food consumed. Asterisks represent significant difference from within-strain saline group, *p<0.05. Data are expressed as mean + 1 SEM. n=7/group
Fig. 2
Fig. 2
Effects of DIPPA in the DB test. a Latency to begin burying. b Total time spent burying the shock probe. c Total time spent immobile. Asterisks represent significant difference from within-strain saline group, *p<0.05 and **p<0.01. Number symbol represents significant difference from SD saline-treated group, #p<0.05 and ##p<0.01. Data are expressed as mean + 1 SEM. n=12–17/group
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