Chronic clomipramine treatment reverses core symptom of depression in subordinate tree shrews

PLoS One. 2013 Dec 2;8(12):e80980. doi: 10.1371/journal.pone.0080980. eCollection 2013.

Abstract

Chronic stress is the major cause of clinical depression. The behavioral signs of depression, including anhedonia, learning and memory deficits, and sleep disruption, result from the damaging effects of stress hormones on specific neural pathways. The Chinese tree shrew (Tupaia belangeri chinensis) is an aggressive non-human primate with a hierarchical social structure that has become a well-established model of the behavioral, endocrine, and neurobiological changes associated with stress-induced depression. The tricyclic antidepressant clomipramine treats many of the core symptoms of depression in humans. To further test the validity of the tree shrew model of depression, we examined the effects of clomipramine on depression-like behaviors and physiological stress responses induced by social defeat in subordinate tree shrews. Social defeat led to weight loss, anhedonia (as measured by sucrose preference), unstable fluctuations in locomotor activity, sustained urinary cortisol elevation, irregular cortisol rhythms, and deficient hippocampal long-term potentiation (LTP). Clomipramine ameliorated anhedonia and irregular locomotor activity, and partially rescued the irregular cortisol rhythm. In contrast, weight loss increased, cortisol levels were even higher, and in vitro LTP was still impaired in the clomipramine treatment group. These results demonstrate the unique advantage of the tree shrew social defeat model of depression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents, Tricyclic / pharmacology*
  • Behavior, Animal / drug effects*
  • Clomipramine / pharmacology*
  • Depression* / blood
  • Depression* / drug therapy
  • Depression* / physiopathology
  • Humans
  • Hydrocortisone / blood*
  • Long-Term Potentiation / drug effects
  • Male
  • Motor Activity / drug effects
  • Social Behavior
  • Stress, Psychological* / blood
  • Stress, Psychological* / drug therapy
  • Stress, Psychological* / physiopathology
  • Tupaiidae

Substances

  • Antidepressive Agents, Tricyclic
  • Clomipramine
  • Hydrocortisone

Grant support

The work was supported by 973 Program from the Ministry of Science and Technology of China (2013CB835103); Strategic Priority Research Program of the Chinese Academy of Science (XDB02020200); the National 863 Project of China (2012AA022402); Chinese Academy of Sciences (KSCX2-EW-R-12, KSCX2-EW-J-23) and National Natural Science Foundation of China (81171294). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.