Behavioral changes in cold-stressed mice related to a central calcium-dependent-catecholamine synthesizing system

An investigation was carried out regarding the mechanism of behavioral changes in mice elicited by cold stress. Cold stress was induced in adult male mice by restraining them from free action for 2 h at 4 degrees C. As the control test, mice were restrained from free action for 2 h at room temperature. The locomotor counts in cold-stressed mice were found to be lower than in controls. The counts in cold-stressed mice were increased by IP pretreatment with EDTA or alpha-methyltyrosine (tyrosine hydroxylase inhibitor), and were further decreased by IP pretreatment with CaCl2. On the other hand, serum calcium and brain calcium levels in cold-stressed mice were increased 15-30 min and 30 min, respectively, after restraint under cold temperatures, and returned to original levels 1 h after restraint. Also, the biochemical and immunohistochemical brain dopamine levels in cold-stressed mice were higher than in control mice. The increment of brain dopamine levels in the control mice was also observed by the administration of CaCl2. Furthermore, the ability of cold stress to enhance the dopamine level in mice brains was attenuated by IP pretreatment with alpha-methyltyrosine. In light of previous reports that central calcium activates catecholamine-synthesizing enzymes via a calmodulin-dependent system, it is suggested that cold stress enhances the brain calcium level, and then increased calcium enhances dopamine synthesis in the brain through a central calcium-dependent catecholamine synthesizing system. Subsequently, increased dopamine induces behavioral changes.