Effects of chronic mild stress (CMS) and imipramine administration, on spleen mononuclear cell proliferative response, serum corticosterone level and brain norepinephrine content in male mice

Psychoneuroendocrinology. 1999 Apr;24(3):345-61. doi: 10.1016/s0306-4530(98)00084-5.


There is increasing evidence that stress and emotional reactions produce changes in various immune processes. These changes may be due to alterations of the stress responses endocrine and for autonomic mediating mechanisms. In order to study such effects, the impact of chronic mild stress (CMS) application, and of subsequent imipramine administration were studied on the spleen mononuclear cell proliferative response period. OFI strain male mice were subjected to 4 or 7 weeks of CMS. The effects of these treatments on serum corticosterone levels and hypothalamic and hippocampal norepinephrine (NE) contents were also assessed. Subjects submitted to CMS had a higher spleen mononuclear cell proliferative response after either treatment duration. Imipramine treatment diminished this response enhancement in CMS exposed animals, but did not alter the proliferative responses of control subjects. Serum corticosterone levels, as well as hypothalamic and hippocampal nonrepinephrine contents did not significantly vary between groups. Taken together, these results suggest that CMSs effects on immune reactivity are not related to serum glucocorticoids or NE changes in these locations associated with the hypothalamic-pituitary- adrenocortical (HPA) axis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology
  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Cell Division / drug effects
  • Chronic Disease
  • Corticosterone / blood*
  • Dietary Sucrose / administration & dosage
  • Hippocampus / metabolism
  • Hypothalamus / metabolism
  • Imipramine / pharmacology*
  • Male
  • Mice
  • Norepinephrine / metabolism*
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology*
  • Stress, Physiological* / immunology
  • Stress, Physiological* / metabolism


  • Adrenergic Uptake Inhibitors
  • Dietary Sucrose
  • Imipramine
  • Corticosterone
  • Norepinephrine