MOUSE ANXIETY MODELS AND AN EXAMPLE OF AN EXPERIMENTAL SETUP USING UNCONDITIONED AVOIDANCE IN AN AUTOMATED SYSTEM - INTELLICAGE

ABSTRACT

Anxiety disorders are the most common forms of mental illness of the adult population of the U.S.A. Use of animal models for anxiety has made an important contribution to clinical and pharmacological anxiety research as well as basic research of the mechanisms involved. We review the current operant conditioning models that are used in anxiety research as well as paradigms using unconditioned fear responses. We then outline how they could theoretically and in practice be adapted to the settings of a novel automated system, the IntelliCage. The IntelliCage is a computer-controlled environment for socially housed mice that automatically records a number of behavioral parameters for each mouse and in addition allows to individually condition and test mice. IntelliCage allows fast and efficient test procedures for evaluating fear responses with a minimum of handling stress and a maximum of standardization. To confirm suitability of the IntelliCage for the study of anxiety, we present results on a modified Vogel water-lick conflict for mice. After 18 hours of water deprivation, mice were exposed to the following three conditions: punished drinking, punished drinking after injection of Diazepam, and punished drinking after injection of saline. The IntelliCage automatically quantified and recorded behavioral parameters indicative of anxiety for each individual. None of the parameters differed between untreated and saline treated control mice. In contrast, animals treated with Diazepam significantly differed from the two other groups in several aspects indicative of decreased anxiety elicited by the aversive stimulus. The results were robust and remained unchanged after correction for individual differences and drug-induced differences in activity. Our study shows that the IntelliCage can be used to assess anxiety and anxiolytic drug effects in a fast and efficient way.

KEYWORDS: Diazepam, Vogel water-lick conflict, anxiolytics, aversive stimulus, automated behavioral observation