Review article
Ethopharmacological studies of anxiolytics and aggression

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Abstract

This paper presents examples of the application of ethopharmacology to the study of aggression. Low doses of benzodiazepines may increase aggression under appropriate conditions. In various animal models in male and female rats and mice the aggression enhancing effects are particularly marked when aggression is inhibited by internal or external events. It is therefore suggested that benzodiazepines have no direct effect on aggression, but modulate inhibitory factors which regulate aggression.

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    During the past 20 years, 44 papers with ethopharmacology in the title have been published (for reviews see Blanchard et al., 2001; Cooper and Hendrie, 1994; Donat, 1991). Originally, the so-called ethopharmacologists studied aggression, social behavior and reproductive behavior (Brain et al., 1991; Meyerson and Hoglund, 1981; Miczek, 1989; Olivier et al., 1991). Obviously mere activity-related parameters will not suffice in those more natural settings.

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    In this test, an animal (the intruder) is placed in the home cage of a conspecific resident; often the resident is isolated prior to the test. The frequency of or latency to attack, and/or other measures of overt aggression or fighting, are recorded (e.g., Thor and Flannelly, 1976; Simon and Whalen, 1986; Parmigiani et al., 1999; Morè, 2008), sometimes in addition to other measures which include both the aggression and the response to it (i.e., “agonistic” behaviour; Olivier et al., 1989, 1991; Alleva, 1993; Pietropaolo et al., 2004; Branchi et al., 2006). As male mice often dominate a shared territory or establish and maintain an exclusive territory in the wild, this test measures natural behaviours in laboratory mice (Miczek et al., 2001, 2007; Latham and Mason, 2004).

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    Aggression research with laboratory rodents has typically focused on males’ behavior, usually employing the resident–intruder test (e.g., Thor and Flannelly, 1976; Brain et al., 1981; Simon and Whalen, 1986), where an intruder is introduced into the home cage of another, usually isolated, animal (the resident). Measures of fighting or overt aggression such as latency to, or frequency of, attack, are taken (e.g., Thor and Flannelly, 1976; Simon and Whalen, 1986; Parmigiani et al., 1999; Morè, 2008), sometimes together with other measures of “agonistic” behavior, which include both the aggression and the reaction to it (Olivier et al., 1989, 1991; Alleva, 1993; Pietropaolo et al., 2004; Branchi et al., 2006). In mice, this paradigm takes advantage of the fact that males will often establish and maintain an exclusive territory or dominate a shared territory under natural conditions (Miczek et al., 2001, 2007; see Latham and Mason, 2004 for a review).

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