Depressive-like behaviour of mice lacking cellular prion protein

Behav Brain Res. 2012 Feb 14;227(2):319-23. doi: 10.1016/j.bbr.2011.03.012. Epub 2011 Mar 23.


Cellular Prion Protein (PrP(C)) is known to mediate a protective role in several neurological conditions such as ischemia and epilepsy. However, so far, little information is available concerning the role of PrP(C) in psychiatric disorders such as depression. Here, we have used PrP(C) null mice to examine a putative role of PrP(C) in depressive-like states. Prion protein null mice exhibited depressive-like behaviour when compared to wild-type mice in both the Forced Swimming Test (FST) and Tail Suspension Test (TST). The clinical antidepressant drug imipramine and the NMDA receptor antagonist MK-801 reversed the depressive-like behaviour observed for knockout mice in the TST. The present data thus indicate that PrP(C) exerts a critical role in modulating the depressive-like state in mice, reinforcing the notion that PrP(C) might be associated with alterations in mood disorder states, and suggests a possible role of PrP(C) as a potential drug target for treating depressive disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology*
  • Depression / drug therapy
  • Depression / genetics
  • Depression / metabolism*
  • Disease Models, Animal
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology*
  • Hindlimb Suspension
  • Imipramine / pharmacology
  • Imipramine / therapeutic use
  • Mice
  • Mice, Knockout
  • Motor Activity / drug effects*
  • Motor Activity / physiology
  • PrPC Proteins / genetics
  • PrPC Proteins / metabolism*
  • Swimming


  • Antidepressive Agents
  • PrPC Proteins
  • Imipramine