Depressive-like behaviour of mice lacking cellular prion protein

Cellular Prion Protein (PrPC 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 PrPC in psychiatric disorders such as depression. Here, we have used PrPC null mice to examine a putative role of PrPC 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 PrPC exerts a critical role in modulating the depressive-like state in mice, reinforcing the notion that PrPC might be associated with alterations in mood disorder states, and suggests a possible role of PrPC as a potential drug target for treating depressive disorders. (C) 2011 Elsevier B.V. All rights reserved.