Measuring normal and pathological anxiety-like behaviour in mice: a review

Abstract

Measuring anxiety-like behaviour in mice has been mostly undertaken using a few classical animal models of anxiety such as the elevated plus-maze, the light/dark choice or the open-field tests. All these procedures are based upon the exposure of subjects to unfamiliar aversive places. Anxiety can also be elicited by a range of threats such as predator exposure. Furthermore, the concepts of 'state' and 'trait' anxiety have been proposed to differentiate anxiety that the subject experiences at a particular moment of time and that is increased by the presence of an anxiogenic stimulus, and anxiety that does not vary from moment to moment and is considered to be an 'enduring feature of an individual'. Thus, when assessing the behaviour of mice, it is necessary to increase the range of behavioural paradigms used, including animal models of 'state' and 'trait' anxiety. In the last few years, many mice with targeted mutations have been generated. Among them some have been proposed as animal models of pathological anxiety, since they display high level of anxiety-related behaviours in classical tests. However, it is important to emphasise that such mice are animal models of a single gene dysfunction, rather than models of anxiety, per se. Inbred strains of mice, such as the BALB/c line, which exhibits spontaneously elevated anxiety appear to be a more suitable model of pathological anxiety.

Adult behavioral and pharmacological dysfunctions following disruption of the fetal brain balance between pro-inflammatory and IL-10-mediated anti-inflammatory signaling

“…This test is widely applied to assess explorative behavior in rodents. 28 Consistent with our previous findings, 16,17 offspring of PolyI:C-treated wt mothers showed a marked reduction in this measure compared to animals born to vehicle-treated wt mothers (Figure 4a). Most importantly, this effect of prenatal PolyI:C exposure was attenuated in macIL-10tg offspring, as offspring of PolyI:C-treated macIL-10tg mothers did not significantly differ from offspring born to vehicle-treated wt mice.…”

Mouse strain differences in the effects of corticotropin releasing hormone (CRH) on sleep and wakefulness

“…The greater effects of CRH and AST on wakefulness and sleep in BALB/cJ mice compared to C57BL/6J mice are consistent with findings that BALB/cJ mice are more reactive in behavioral tests of anxiety (Belzung and Griebel, 2001;Tang et al, 2002b) and also show greater alterations in sleep in response to a number of stressors (Wurbel et al, 1998;Sanford et al, 2003a;2003b;2003d). Thus, strain differences in the effects of CRH and AST may be linked to underlying differences in the CRH system that may also be involved in the relative responsiveness to stressors in C57BL/6J and BALB/cJ mice.…”

“…Behavioral data suggest that C57BL/6J mice are a less "anxious" or reactive strain, and that BALB/cJ are a more "anxious" or reactive strain (Tang et al, 2002). Indeed, BALB/cJ mice have been suggested to exhibit pathological anxiety (Belzung and Griebel, 2001;Tang et al, 2002) whereas C57BL/6J mice show an intermediate phenotype in most behaviors (Crawley, 1999) and are often used in strain comparisons. Moreover, mice display greater changes in REM than in NREM after exposure to novelty (Tang et al, 2004; and after experiencing stressors such as fearful stimuli (Sanford et al, 2001;Sanford et al, 2003a;2003b;2003d;Liu et al, 2004) and restraint (Wurbel et al, 1998;Meerlo et al, 2001;Liu et al, 2004).…”

Effect of chronic stress during adolescence in prefrontal cortex structure and function

“…Thigmotaxis is associated with fear of open spaces and is a valid measure of anxiety and risk evaluation [47]. Thigmotaxis was evaluated in a wooden apparatus (0.60 × 0.60 × 0.35 m) and the dependent variable was the amount of time the animal spent away from a 0.05 m wide strip close to the wall.…”

“…More specifically, we address the effects of chronic stress both on the spatial-temporal distribution of PNN + neurons in the PFC and on tests of executive function during adolescence. To test maladaptive executive function associated with deficits in working memory and bad judgment in decision making we used the spontaneous alternation [41][42][43][44][45][46] and the open field test [47], respectively.…”