Comparison of the kappa-opioid receptor antagonist DIPPA in tests of anxiety-like behavior between Wistar Kyoto and Sprague Dawley rats.
BACKGROUND
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.
Carr
Gregory V
GV
Department of Psychiatry, University of Pennsylvania, 125 South 31st Street, Room 2204, Philadelphia, PA, USA.
Lucki
Irwin
I
D000081:Acetamides / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D017879:Isothiocyanates / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D013045:Species Specificity
D000081:Acetamides; D014151:Anti-Anxiety Agents; D017879:Isothiocyanates; D017473:Receptors, Opioid, kappa; C087549:2-(3,4-dichlorophenyl)-N-methyl-N-(1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl)acetamide