Anxiety-Related Behaviors in Mice (2008)

Human anxiety disorders are broadly grouped according to symptomology and responsiveness to pharmacological and psychological treatment [1,2]. Generalized anxiety disorder and panic disorder are the two primary classifications of pathological anxiety in humans. The distinguishing feature of generalized anxiety disorder is a pervading sense of unrealistic worry about everyday life situations. In contrast, panic attacks constitute the primary symptom of panic disorder. These events are characterized as sudden, extreme fear accompanied by autonomic nervous system arousal [3].Similar changes in physiological indicators and behavioral responses to fear and painful stimuli in humans and other animals suggest the possibility of homologous or analogous, ethologically motivated defensive responses [4–10] In the description of human anxiety disorders, the concepts of “state” and “trait” anxiety have a long history. However, it is only recently that these concepts have been suggested as a means of differentiating situational anxiety-like behavior in rodents from anxiety that transcends the situation and is an enduring condition in the animal [11]. The former is the focus of the rodent behavioral tests reviewed in this chapter. Procedures are designed to trigger ethologically relevant conflict or conditioned behaviors. The latter is most often associated with selective breeding, e.g., the high versus low anxiety-related traits in the high anxiety-related behavior (HAB) versus low anxiety-related behavior (LAB) rats [12], inbred mouse strains such as BALB/c, and mice with relevant targeted gene mutations [13,14].In an attempt to model human pathological anxiety in rodents, a wide range of behavioral testing paradigms have been developed [8,15–19]. Many of these tests induce a fearful response through an aversive event or anticipated aversive event. Others integrate an approach–avoidance conflict designed to inhibit an ongoing behavior that is characteristic for the animal, such as contrasting the tendency of mice to engage in exploratory activity or social investigation against the aversive properties of an open, brightly lit, or elevated space. The premise that basic physiological mechanisms underlying fear in rodents can be equated to similar mechanisms operating in humans provides a degree of face validity for these paradigms [7,9,10]. In rodents, these responses are deemed appropriate and adaptive for the current conditions, whereas in humans, anxiety disorders constitute maladaptive or pathological responses to the existing situation. Further exploration of rodent neuroanatomy and neurochemistry involved in fear extinction and inhibition of conditioned fear could offer important insights into effective targets for novel pharmacological treatment of pathological human anxiety [20].Although rats have been the rodent of choice for much of the preclinical research on anxiety-like behavior, recent technical advances in molecular genetics have placed the mouse in the forefront of neuropsychiatric research [7,13,21–26]. This has resulted in the adaptation of many well-validated behavioral tests of anxiety from rats to mice, with varying degrees of success. This chapter offers a sampling of well-established tests of anxiety-like behavior in mice that use an ethological conflict. The interested researcher is directed to the classic source literature for more information on other types of anxiety-based tests, including conditioning paradigms [27–29], punishment-induced conflict tests [18,19,30,31], developmental models [32,33], and aversive tests [5,34].