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

Abstract

Anxiety is one of the most prominent psychiatric disorder related to a common stress. The success of pharmacological treatments for this disorder has been dampened by various factors, including resistance to treatment and adverse effects of the drugs used. Although the themes of stress and anxiety have long been a topic of investigation, current anxiolytic drugs are only based on pharmacological interactions with classic neurotransmitters. Accordingly, we investigated possible alternative mechanisms that might lead to development of new classes of anxiolytic drugs using SART-stressed animals.Corticotropin-releasing factor (CRF), a hypothalamic peptide consisting of 41 amino acids, is a key mediator of mammalian endocrine, behavioral, autonomic, and immune responses to stress. 1,2) Within the hypothalamic-pituitaryadrenal (HPA) axis, CRF is the principal regulator of pituitary adrenocorticotropic hormone (ACTH) and adrenal glucocorticoid secretion in responses to stressful stimuli. Basic research studies indicate that elevated central CRF levels are involved in the etiology of stress-related psychiatric, physiological and behavioral disorders.3) Central administration of CRF exerts potent anxiogenic effects in experimental animals.4) Clinical studies also demonstrate that CRF is implicated in anxiety. 5,6) We have investigated the effects of stress on physiological conditions and on emotions using SART (specific alternation of rhythm in temperature) stress, 7) which is known as a model of autonomic imbalance.8) The stressful situation is created 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 to go outdoors. Animals exposed to SART stress show adverse biological events 9-11) and physiological abnormalities. 7,12,13) Furthermore, a series of our behavioral studies using SARTstressed animals demonstrated that environmental stress induces anxiety-like behavior. 14-16) 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.14-16) This evidence suggests that SART-stressed animals may be in a state of anxiety.As SART stress causes anxiety-like behavior in mice and rats in several tests, we turned our attention to the possibility that CRF may be involved in the stress and anxiety of SARTstressed mice. In the present study, we determined whether inhibition of CRF receptor function using a-helical CRF as a specific CRF receptor antagonist could normalize anxietylike behavior caused by SART stress using forced swimming (FS) test and elevated plus-maze (EPM) test.The FS test is a well-known screening model for antidepressants developed by Porsolt et al. 17,18) At first, they suggested that the characteristic immobility observed in the FS test reflect...

Processed Aconite Root Prevents Cold-Stress-Induced Hypothermia and Immuno-Suppression in Mice

“…However, chronic exposure to cold stress disturbs homeostasis, gradually resulting in an unstable internal environment and increased risk of illnesses. In animal experiments, chronic cold stress reduced the core body temperature, 2) induced hypertension, 3,4) anxiety-like behavior, 5) and suppressed immune functions, including the activity of natural killer (NK) cells 6) and antibody production. 7) Therefore, cold stress could lead to the development of dysfunctions in some organs.…”

Evaluation of Anti-Anxiety Activity of Anacyclus Pyrethrum

“…Mice treated with ethanol extract of A. pyrethrum showed increase in the time spent in the light compartment and also changes in the numbers of shuttle crossings, confirming the activity upon the main anxiolytic parameter. The observed anxiolytic effect of the title plant may be due to the agonistic effect on GABA/benzodiazepine receptor complex, or 5-HT1A receptor or antagonize the 5-HT1B receptor 13,14 .…”

Behavior and Brain Gene Expression Changes in Mice Exposed to Preimplantation and Prenatal Stress

“…The observed discrepancy between Crfr2 expression levels and behavior on open arm may be due to a compensatory adaptive stress response of IVF mice to a second hit represented by the LP/HF diet or could be related to the multifaceted role played by the CRF in the stress response. 46,47 In fact, CRF activation is a common response to a variety of stressors. 48 Administration of CRF in the brain of rats is correlated with reduced exploratory activity and enhanced anxiety 49,50 mediated by CRFR1.…”