Depressive-like behaviour of mice lacking cellular prion protein

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.