Prototypical anxiolytics do not reduce anxiety-like behavior in the open field in C57BL/6J mice

Area of Science:

• Neuroscience
• Behavioral Pharmacology
• Animal Models of Disease

Background:

• Anxiety disorders present treatment challenges, with suboptimal efficacy and side effects of current therapies.
• Animal models are crucial for understanding anxiety and evaluating potential anxiolytics.
• The open field (OF) test is a widely used assay for anxiety-like behavior, but its validation in mice requires further investigation.

Purpose of the Study:

• To assess the efficacy of chlordiazepoxide (CDP) and diazepam (DZ) in the OF test for C57BL/6J mice.
• To determine if increasing OF illumination affects anxiolytic drug responses.
• To evaluate the predictive validity of the OF test for anxiolysis across different mouse strains and behavioral assays.

Main Methods:

• Administered prototypical benzodiazepines (chlordiazepoxide, diazepam) and buspirone to C57BL/6J mice in the OF.
• Tested the effects of varied illumination and anxiogenic agent (mCPP) in the OF.
• Evaluated CDP in BALB/cJ and DBA/2J mice, and CDP/DZ in other anxiety models (EPM, EZM, LD, SIH).
• Conducted pharmacokinetic studies to ensure drug bioavailability.

Main Results:

• Chlordiazepoxide and diazepam did not alter center time in the OF across tested doses and illumination levels.
• Buspirone also failed to increase center time, while mCPP increased it.
• CDP showed no effect in BALB/cJ or DBA/2J mice; CDP was ineffective in EPM, EZM, and LD tests.
• DZ reduced stress-induced hyperthermia, but pharmacokinetic data indicated adequate CDP levels for anxiolysis.

Conclusions:

• Center time in the OF test lacks predictive validity for anxiolysis in the studied inbred mouse strains.
• The OF test's utility for assessing anxiolytic efficacy in mice, particularly with benzodiazepines, is questionable.
• Further validation and exploration of alternative behavioral assays are needed for reliable anxiety research in mice.