Chronic social stress during adolescence: interplay of paroxetine treatment and ageing

Neuropharmacology. 2013 Sep:72:38-46. doi: 10.1016/j.neuropharm.2013.03.035. Epub 2013 Apr 16.

Abstract

Exposure to chronic stress during developmental periods is a risk factor for a number of psychiatric disorders. While the direct effects of stress exposure have been studied extensively, little is known about the long-lasting effects and the interaction with ageing. The same holds true for the treatment with selective serotonin reuptake inhibitors (SSRIs), which have been shown to prevent or reverse some stress-induced effects. Here, we studied the direct and long-lasting impact of chronic social stress during adolescence and the impact of chronic treatment with the SSRI paroxetine in adulthood and aged animals. Therefore, male CD1 mice at the age of 28 days were subjected to 7 weeks of chronic social stress. Treatment with paroxetine was performed per os with a dosage of 20 mg/g BW. We were able to reverse most of the effects of chronic social stress in adult mice (4 months old) and to some extend in aged animals (15 months old) with the SSRI treatment. Especially the regulation of the HPA axis seems to be affected in aged mice with a shift to the use of vasopressin. Our results demonstrate that chronic stress exposure and antidepressant treatment at the end of the developmental period can have a significant and long-lasting impact, highly relevant for healthy ageing.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / drug effects
  • Aging*
  • Animals
  • Arginine Vasopressin / genetics
  • Arginine Vasopressin / metabolism
  • Body Weight / drug effects
  • Chronic Disease
  • Corticosterone / blood
  • Corticotropin-Releasing Hormone / blood
  • Corticotropin-Releasing Hormone / genetics
  • Dexamethasone
  • Disease Models, Animal
  • Exploratory Behavior / drug effects
  • Gene Expression Regulation / drug effects
  • Longitudinal Studies
  • Male
  • Mice
  • Paroxetine / therapeutic use*
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Social Isolation / psychology*
  • Stress, Psychological / blood
  • Stress, Psychological / drug therapy*
  • Thymus Gland / drug effects

Substances

  • Receptors, Glucocorticoid
  • Serotonin Uptake Inhibitors
  • Arginine Vasopressin
  • Paroxetine
  • Dexamethasone
  • Corticotropin-Releasing Hormone
  • Corticosterone