Mouse defensive behaviors: pharmacological and behavioral assays for anxiety and panic

The natural defensive behaviors of laboratory mice have been evaluated in b oth seminatural and highly structured situations; and characterized in term s of eliciting stimuli, response to pharmacological agents, behavior patter ns, and outcome or effect on the social and physical environment. The defen se patterns of laboratory mice and rats are generally similar, but mice sho w risk assessment on initial exposure to highly threatening stimuli while r ats do not, while rats display alarm vocalizations, missing in mice. Quanti tative differences in freezing and flight fur laboratory mice and rats appe ar to largely reflect domestication effects, with wild mice and rats more s imilar to each other. This nexus of detailed within-species and comparative data on defense patterns makes it possible to reliably elicit specific def enses in mice or rats in an experimental context, providing well-validated assays of the natural defensive behaviors themselves, as opposed to 'models ' of defense. The mouse-rat. comparisons indicate considerable cross-species generality f or these defense patterns, as does a scattered but considerable literature on other mammalian species, generally involving field studies and typically focusing on those aspects of defensive behavior that are visible at a dist ance, such as vigilance, or flight. Although potential homologies between n ormal mouse and human defense systems should ideally involve all four patte rn components (stimulus, organismic factors, response characteristics, outc ome), predictive validity in terms of response to drugs active against spec ific defensive psychopathology is the most extensively investigated of thes e. Flight, as measured in the Mouse Defense Test Battery shows a consistent ly appropriate response to panicolytic, panicogenic, and panic-neutral drug s, while some other predictive 'panic models' (dPAG-stimulation; DMH-inhibi tion; possibly conditioned suppression of drinking paradigms) also elicit a nd (indirectly) measure behaviors potentially related to flight. Models unr elated to flight (e.g. ultrasonic vocalization to conditioned stimuli); or for which flight elements may a relatively minor contributor to the behavio r measured Elevated T-maze) are less predictive of panicolytic or panicogen ic action. These findings indicate that natural defensive behaviors provide a well-characterized pattern for analysis of effects of genetic or other p hysiological manipulations in the mouse, and may also serve as a model for analysis of defense-related human psychopathology. (C) 2001 Elsevier Scienc e Ltd. All rights reserved.