Neurochemical changes in mice following physical or psychological stress exposures.
An investigation on the mechanism of neurochemical changes in physically or psychologically stressed mice was carried out. Physical stress was induced by electric foot shocks (2 mA for 5 s at 30-s intervals), and psychological stress was induced by emotional stimuli from electric foot-shocked mice using a communication box. The serum and brain calcium levels and immunohistochemical brain dopamine levels increased, and the ethanol-induced sleeping time was prolonged following exposure to these stimuli. The effects of electric foot shocks on these physiological parameters were greater than those of emotional stimuli. In the psychologically stressed mice, serum and brain calcium levels significantly increased 15 and 60 min, respectively, after the start of exposure to stimuli. Also, the immunohistochemical dopamine levels in the neostriatum and nucleus accumbens regions after 60 min of exposure to psychological stress were higher by 23% (P < 0.01) and 27% (P < 0.01), respectively, than those in unstressed control mice. Moreover, the ethanol-induced sleeping time was prolonged by approximately 60-100% (P < 0.01) in mice exposed to psychological stress for 30-120 min. The effect of emotional stimuli to prolong the ethanol-induced sleeping time was inhibited by intracerebroventricular administration of W-7 (a calmodulin antagonist) or alpha-methyltyrosine (an inhibitor of tyrosine hydroxylase). In light of previous reports that calcium activates dopamine synthesis in the brain via a calmodulin-dependent system, it is suggested that physical or psychological stimuli induce an increase in the brain calcium level, and this increased calcium level in turn enhances dopamine synthesis in the brain. Subsequently, an increased dopamine level induces various physiological changes related to stress-dependent phenomena.
Institute of Medical Science, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. dsutoo@md.tsukuba.ac.jp
Den'etsu
D
Sutoo
Kayo
K
Akiyama
D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D002118:Calcium / Q000097:blood / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004597:Electroshock; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D012890:Sleep / Q000187:drug effects; D013312:Stress, Physiological / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D002147:Calmodulin; D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D013449:Sulfonamides; D000431:Ethanol; C017967:W 7; D019805:alpha-Methyltyrosine; D014446:Tyrosine 3-Monooxygenase; D002118:Calcium; D004298:Dopamine