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

Abstract

The natural defensive behaviors of laboratory mice have been evaluated in both seminatural and highly structured situations; and characterized in terms of eliciting stimuli, response to pharmacological agents, behavior patterns, and outcome or effect on the social and physical environment. The defense patterns of laboratory mice and rats are generally similar, but mice show risk assessment on initial exposure to highly threatening stimuli while rats do not, while rats display alarm vocalizations, missing in mice. Quantitative differences in freezing and¯ight for laboratory mice and rats appear to largely re¯ect domestication effects, with wild mice and rats more similar to each other. This nexus of detailed within-species and comparative data on defense patterns makes it possible to reliably elicit speci®c defenses in mice or rats in an experimental context, providing well-validated assays of the natural defensive behaviors themselves, as opposed tò models' of defense.The mouse±rat comparisons indicate considerable cross-species generality for these defense patterns, as does a scattered but considerable literature on other mammalian species, generally involving ®eld studies and typically focusing on those aspects of defensive behavior that are visible at a distance, such as vigilance, or¯ight. Although potential homologies between normal mouse and human defense systems should ideally involve all four pattern components (stimulus, organismic factors, response characteristics, outcome), predictive validity in terms of response to drugs active against speci®c defensive psychopathology is the most extensively investigated of these. Flight, as measured in the Mouse Defense Test Battery shows a consistently appropriate response to panicolytic, panicogenic, and panic-neutral drugs, while some other predictive`panic models' (dPAG-stimulation; DMH-inhibition; possibly conditioned suppression of drinking paradigms) also elicit and (indirectly) measure behaviors potentially related to¯ight. Models unrelated to¯ight (e.g. ultrasonic vocalization to conditioned stimuli); or for which¯ight elements may a relatively minor contributor to the behavior measured (Elevated T-maze) are less predictive of panicolytic or panicogenic action. These ®ndings indicate that natural defensive behaviors provide a well-characterized pattern for analysis of effects of genetic or other physiological manipulations in the mouse, and may also serve as a model for analysis of defenserelated human psychopathology. q 2001 Elsevier Science Ltd. All rights reserved. The recent explosion of genetic techniques and genetically modi®ed animals has greatly exacerbated the need for comprehensive, natural, models or assays of behavior that are relevant to mice, the mammalian species of choice for genetic research [25]; and has additionally focused attention on issues of construction and validation of these tests.Minimally, a behavioral model/assay should enable the reliable elicitation and measurement of a qualitatively consistent behavior pattern for ...

The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic

“…However, a recent attempt to determine ''first-choice'' defensive behaviors to threat stimuli and situations described in scenarios provides considerable support for a view that people utilize flight, hiding, freezing, defensive threat/attack, and risk assessment extensively in dealing with threat. Moreover, hypotheses concerning the relationship of threat stimulus/situational characteristics and specific defensive behaviors, based on rodent experiments, were strongly supported by this study of human response choices (Blanchard et al, 2001). While this study says nothing about the biological mechanisms involved, it does provide some assurance that despite the enhanced array of human social, verbal, and technological defenses, there remains considerable conservation of infrahuman mammalian defenses in the normal human defense repertory.…”

“…These are species-typical (i.e. typically expressed by individuals of those species under appropriate circumstances) but not species-specific: they occur in much the same form across a variety of mammalian species (Blanchard et al, 2001). The statement that these are unconditioned reflects that each behavior can be elicited in wild rats or wild mice (and with partial exceptions to be noted later) in laboratory or domesticated strains of rats and mice without prior relevant experience (see Blanchard, 1997 for review of behavioral analyses).…”

Effects of intrinsic aerobic capacity, aging and voluntary running on skeletal muscle sirtuins and heat shock proteins

“…handling of the animal and estrous cycle. Handling is known to 521 have a stress effect on rats and it can cause a series of behavioral and physiological responses, 522 such as flight response, freezing response, increase in heart rate, urination and increase in 523 plasma glucocorticoid levels (Rodgers et al 1997, Blanchard, Griebel & Blanchard 2001. It 524 is known that HCRs have stronger response to stress, and this can be observed also in 525 elevated corticosterone level in blood in HCRs compared to LCRs (Waters et al 2010).…”

Mouse chronic social stress increases blood and brain kynurenine pathway activity and fear behaviour: Both effects are reversed by inhibition of indoleamine 2,3-dioxygenase

“…In human and rodent, the US is usually mildmoderate electroshock (Fullana et al, 2015;Phelps and LeDoux, 2005), and visual and auditory CS are typically used in human and rodent, respectively (Fullana et al, 2015;Phelps and LeDoux, 2005). In humans, CS responsiveness is measured using skin conductance and subjective report (Fullana et al, 2015), and in rodents the defensive behaviour of complete 5 inactivity, or "freezing", is used (for review: (Blanchard et al, 2001;Maren and Quirk, 2004;Phelps and LeDoux, 2005)). Rodent fear conditioned freezing provides a model system for investigating the neurobiology of negative valence processing, including CS-US learning, consolidation and recall of CS-US memory, and activation of conditioned freezing response (LeDoux, 2000;Rescorla, 1988;Wolff et al, 2014).…”