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 ...