Exploratory behavior models of anxiety in mice

Area of Science:

• Neuroscience
• Pharmacology
• Behavioral Science

Background:

• Anxiety disorders are prevalent, necessitating effective pharmacological treatments.
• Developing novel anxiolytic compounds requires reliable preclinical screening models.
• Mouse models are frequently used to assess the efficacy of potential anxiolytic drugs.

Purpose of the Study:

• To review parameters of exploratory behaviors in mice sensitive and specific to anxiolytic drugs.
• To evaluate the utility of mouse models for predicting anxiolytic drug efficacy.
• To establish the pharmacological specificity of behavioral tests for anxiolytics.

Main Methods:

• Analysis of behavioral responses to agonists of the benzodiazepine binding site (e.g., chlordiazepoxide, diazepam).
• Assessment of exploratory behaviors in paradigms like the hole-board, light-dark transition, and social interaction tests.
• Evaluation of drug specificity using non-anxiolytic psychoactive compounds and benzodiazepine antagonists (e.g., Ro-15-1788).

Main Results:

• Benzodiazepine agonists significantly increased exploration, social interaction, novel food consumption, and punished crossings.
• Anxiolytic effects were detected at clinically relevant benzodiazepine doses.
• The hole-board and light-dark transition tests demonstrated pharmacological specificity, avoiding false positives from non-anxiolytic drugs.
• Anxiolytics reduced open field behaviors and isolation-induced aggression, potentially within sedative-hypnotic ranges.
• Benzodiazepine antagonists showed limited antagonist properties in mouse models, suggesting potential differences with rat models.

Conclusions:

• Mouse exploratory behavior paradigms are sensitive and specific for detecting anxiolytic drug effects.
• These models offer a wide separation between anxiolytic and sedative doses, making them valuable predictive screens for novel anxiolytic compounds.
• Mouse models appear to rely on the disinhibition of natural exploratory tendencies by anxiolytic treatments.