The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic
Section snippets
Phenomenological status
The unconditioned defensive behaviors of rodents appear to consist of at least the following: flight, hiding, freezing, defensive threat, defensive attack, and risk assessment. Undoubtedly, more such defensive behaviors remain to be discovered or analyzed. 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 Fear/Defense Test Battery
The same research that described defensive behaviors in laboratory rodents also yielded the first test situations for analysis of drug effects on these same responses. In particular, a long (6 m), oval runway apparatus utilizing a human experimenter as the threat stimulus was developed in order to permit the adequate expression of flight behaviors in wild rats (Rattus norvegicus). These animals, both wild-trapped or first-generation laboratory-bred, show a very high probability of rapid flight
The Mouse Defense Test Battery: an experimental model of different emotional states: evidence from factor analysis
Factor analyses are commonly used to describe the relationship between different variables and, consequently, to identify specific indices or factors such as anxiety and locomotor activity. Thus, the question whether the different defensive responses elicited in the Mouse Defense Test Battery provide different measures of the same state or measure distinct states of defensiveness, fear, or anxiety has been approached by performing a factor analysis of the various behavioral defense reactions
GABAA–benzodiazepine receptor ligands
Introduced over 40 years ago, benzodiazepines quickly became the most widely used of all psychotropic drugs. Their marked anxiolytic, hypnotic, anticonvulsant, and muscle relaxant properties and their relative safety rapidly elevated benzodiazepines to the treatment of choice for common and recurrent conditions such as generalized anxiety disorder, muscle tension, and insomnia. However, these compounds have come under critical review because of the problems of drug dependence, tolerance,
Selective and nonselective 5-HT-interacting drugs
Although benzodiazepines remain the mainstay of the treatment of anxiety disorders, preclinical research in this area has mainly focused on compounds modulating 5-HT (5-hydroxytryptamine) neurotransmission during the last two decades Griebel, 1995, Griebel, 1997. However, it is somewhat surprising to note that after all this research effort, only a few direct 5-HT-acting compounds have been launched for the treatment of generalized anxiety disorder (i.e. buspirone and tandospirone) Barradell
Neuropeptides and neuropeptide receptor ligands
The treatment of anxiety disorders remains an active area of research, and anxiolytic drug discovery focuses more and more on the involvement of neuroactive peptides in the modulation of anxiety behaviors. Among these, corticotropin-releasing factor (CRF), cholecystokinin (CCK), and tachykinins (substance P and neurokinin A and B) have been the most extensively studied, but the involvement of other neuroactive peptides such as neuropeptide Y, arginine vasopressin, nociceptin/orphanin FQ, and
Summary
The Mouse Defense Test Battery was specifically developed on the basis of previous rat defense test batteries. These, the Fear/Defense Test Battery and Anxiety/Defense Test Battery, had also provided information on specific defense effects of a number of anxiolytic or potentially anxiolytic drugs, effects that could be, and overwhelmingly have been, confirmed by results of Mouse Defense Test Battery drug studies. Analyses of the behaviors measured in the Mouse Defense Test Battery suggest four
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