Relations between open‐field, elevated plus‐maze, and emergence tests in C57BL/6J and BALB/c mice injected with GABA‐ and 5HT‐anxiolytic agents

Abstract

Two 5HT(1A) receptor agonists and chlordiazepoxide were examined in open-field, elevated plus maze, and emergence tests. At doses with no effect in the open-field, chlordiazepoxide increased open and open/total arm visits as well as open arm duration in the elevated plus maze, whereas 5HT(1A) receptor agonists showed an anxiolytic response on a single measure. The anxiolytic action of chlordiazepoxide was limited to the less active BALB/c strain. Unlike the 5HT(1A) receptor agonists, chlordiazepoxide was also anxiolytic in the emergence test, once again only in BALB/c and not C57BL/6J mice. Significant correlations were found between emergence latencies and specific indicators of anxiety in the elevated plus-maze in chlordiazepoxide-treated but not in mice treated with buspirone and 8-OH-DPAT. These results indicate that elevated plus-maze and emergence tests depend on benzodiazepine receptors. In contrast, 5HT(1A) receptor agonists were ineffective in the emergence test and no correlation was found between emergence latencies and specific indicators of anxiety in the elevated plus-maze. Though superficially similar, the emergence test seems to tap into a partially separate facet of anxiety.

The effect of chlordiazepoxide on measures of activity and anxiety in Swiss-Webster mice in the triple test

“…CDZ also increased the number of transitions made from the dark into the light compartments of the LDB. The effects of CDZ on mice in the EPM and LDB in the present study are consistent with previous reports (Cryan and Holmes, 2005;Holmes et al, 2002;Lalonde and Strazielle, 2009). …”

“…CDZ or saline were administered intraperitoneally at a volume of 10 ml/kg of body weight 30 min before testing. The doses were based on previous reports that show anxiolytic effects (File, 1990;Holmes et al, 2001;Lalonde and Strazielle, 2009). There were 16 mice (8 males, 8 females) in each of four groups.…”

Decreased anxiety in juvenile rats following exposure to low levels of chlorpyrifos during development

“…On PND25, each rat was subjected to an emergence test similar to that described by Smith et al (1998) and Lalonde and Strazielle (2008; 2009; 2010) with some modifications. The behavioral arena was a clear plexiglass open-field (28 × 28 × 46 cm).…”

Prototypical anxiolytics do not reduce anxiety-like behavior in the open field in C57BL/6J mice

“…We used a 30-minute interval between drug administration and behavioral testing based on published protocols (Angrini et al, 1998;Birkett et al, 2011;Choleris et al, 2001;Heredia et al, 2013a;Lalonde and Strazielle, 2010;Salomons et al, 2012;Seredenin et al, 1990Seredenin et al, , 2013. Our PK studies determined that peak CDP concentration occurred prior to testing.…”

“…Studies of classical anxiolytics in mice in the OF typically report drug-induced locomotor and rearing effects but often do not report or observe an increase in time in the center of the arena (Birkett et al, 2011;Crabbe et al, 1998;Crawley, 1981;Fahey et al, 1999;Heredia et al, 2013a;Lalonde and Strazielle, 2010;Lopez et al, 1988;Novas et al, 1988;Seredenin et al, 1990). The lack of evidence for changes in center time in response to anxiolytics suggests that this measure may not be a valid gauge of anxiety in mice.…”