Objective To observe the changes of cyclic nucleotide system in hypothalamus and expression of c-fos protein in different brain areas and nucleus of rats with chronic psychological stress and effects of Chinese formula-JWSNS.MethodsBondage was adopted to established the rat model of chronic psychological stress. The contents of cAMP and cGMP were detected by radio-immunity analysis, and expression of c-fos protein was detected by immunohistochemistry method. ResultsThe contents of cAMP and cGMP in hypothalamus increased significantly (1.309±0.62 and 0.136±0.05)(P <0.01).C-fos protein could express widely and consecutively in hippocampus, cortex, amygdaloid complex, hypothalamus including paraventricular nucleus (Pa), periventricular nucleus (Pe) and arcuate nucleus (Arc), especially in cortex and amygdaloid complex. JWSNS can decrease the content of cAMP, cGMP(0.877±0.05 and 0.051±0.02), and the number of fos like immunoreactive neuron and expressions of c-fos protein in those brain areas and nucleus.ConclusioncAMP, cGMP.and c-fos were concerned with the mechanism of chronic psychological stress; JWSNS maybe regulate chronic psychological stress reaction by affecting cyclic nucleotide system.and c-fos.