Anxiety-Like Behavior in Elevated Plus-Maze Tests in Repeatedly Cold-Stressed Mice

Abstract

ABSTRACT-To clarify the relationship between SART (specific alternation of rhythm in temperature) stress (repeated cold stress) and anxiety, the effects of various types of stress on the behavior of mice were studied in elevated plus-maze tests and then the effects of anxiolytics were evaluated. The percentage of time spent in the open arms of the plus-maze apparatus decreased in mice subjected to SART stress without change in the total number of arm entries. No change was noted in mice subjected to other stresses, such as 1-h, 2-day and 5-day cold stress and 1-h, 15-h and 5´15-h restraint stress. The reduction in the percentage of time spent in the open arms caused by SART stress was inhibited by single and repeated administrations of diazepam and alprazolam and by a single administration of buspirone, which have no influence on the percentage of time spent in the open arms in nonstressed mice, but not by flumazenil, WAY-100635 and chronic treatment with buspirone. The effects of diazepam and buspirone were antagonized by flumazenil and WAY-100635, respectively. The behavior of SART-stressed mice in the plus-maze would thus appear to arise from anxiety, to which benzodiazepine and serotonin receptors are related, but the diazepam binding inhibitor, an endogenous anxiogenic protein, is not. Thus SART-stressed animals may be useful for investigating the psychopharmacological and neuropharmacological basis of anxiety.Keywords: Elevated plus-maze, Stress, SART stress, Anxiety, Repeated cold stressThe relationship between anxiety and stress is a point of much interest. Chronic stress induces mood disorder-like behavior in mammals including humans, and it may be a main factor in the development of anxiety (1, 2). Exposure to various types of stress results in anxiogenic behavior in tests for anxiety in animals. Social stress (3, 4), inescapable electric foot-shocks (5), immersion in water (6) and exposure to unpleasant smells such as cat odor (7) reduce the exploration of open spaces in an elevated plus-maze and cause reduction in social interactions in mice (7, 8).The behavioral characteristics of animals exposed to SART (specific alternation of rhythm in temperature) stress (9 -13) were studied. SART stress (14) is stimulation by repeated and sudden changes in environmental temperature from room temperature to cold temperature, an event that may be encountered by humans in daily life such as in early spring or autumn or when leaving an air-conditioned room in summer or a heated room in winter. Animals exposed to SART stress are a model of autonomic imbalance (15) and show adverse biological events (16 -19) and physiological abnormalities (14, 20 -23). Abnormal behavior is shown in open-field (9), step-down (11) and forced swimming tests (12, 13). This abnormal behavior is normalized by antianxiety agents (9, 12, 13). Changes in neurotransmitters related to abnormal behavior have been noted (24 -26). Certain aspects of these abnormalities are thought to be related to anxiety.To clarify the relationship between SART ...

Chronic Unpredictable Stress Induces a Cognitive Deficit and Anxiety-Like Behavior in Rats that is Prevented by Chronic Antidepressant Drug Treatment

“…As in our own previous work and that of others (eg, Griebel et al, 1997;Hata et al, 2001;Khoshbouei et al, 2002), OTR for time was found to be the more consistent and reliable measure of open-arm exploration, and a more sensitive indicator of anxiogenic response to CUS, but similar effects were also seen with OTR for Entries. This combined effect of a decrease in cognitive capability, in particular cognitive flexibility, together with a basal state of anxiety-like behavior induced by CUS is consistent with the changes in cognition and anxiety seen in major depressive disorder.…”

Mice Lacking the Serotonin Transporter Exhibit 5-HT1A Receptor-Mediated Abnormalities in Tests for Anxiety-like Behavior

“…These doses of WAY 100635 had no significant effect on plus-maze anxiety-like behavior in +/+ controls either in this experiment or in our pilot studies. At the doses presently tested, systemic administration of WAY 100635 and other selective antagonists, such as mPPI, has been found to exert anxiolytic-like effects in the various rodent tasks, including the elevated plus maze, in some studies (eg Cao and Rodgers, 1997a, b;Griebel et al, 1999Griebel et al, , 2000, but not others (eg File et al, 1996;Collinson and Dawson, 1997;Mendoza et al, 1999;Hata et al, 2001; for reviews see Griebel, 1995;Cao and Rodgers, 1997a, b;Griebel et al, 1999). One possible reason for this variability is that the effects of 5-HT 1A receptor antagonists will depend upon basal serotonergic tone and baseline anxietylike behavior evoked in a given test situation, which will vary somewhat across laboratories (Rodgers and Cao, 1999).…”

A Role for Corticotropin-Releasing Factor in Repeated Cold Stress-Induced Anxiety-Like Behavior during Forced Swimming and Elevated Plus-Maze Tests in Mice

“…These studies have provided insight into the complex roles of CRF 1 and CRF 2 in the regulation of emotional behavior, HPA axis 16) Diazepam, alprazolam and buspirone improved the abnormal and anxiety-like behavior in SART-stressed mice in the EPM test without any influence on unstressed mice. 16) In this study, CRF produced a decrease in the time spent on the open arms in unstressed and SART-stressed mice. a-Helical CRF produced an increase in the time in SART-stressed mice, but had no effect on unstressed mice.…”

“…7,12,13) Furthermore, a series of our behavioral studies using SARTstressed animals demonstrated that environmental stress induces anxiety-like behavior. [14][15][16] The anxiety-like behaviors caused by SART stress are normalized by anxiolytic agents such as diazepam, alprazolam, benzodiazepine-receptor agonists, and buspirone, a selective 5-HT 1A serotonin-receptor agonist. [14][15][16] This evidence suggests that SART-stressed animals may be in a state of anxiety.…”