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.

► In this study, we examine the role of cellular prion protein in animal behavior. ► We show that mice lacking cellular prion protein exhibit depressive like behavior. ► We present evidence that the depressive like state can be reversed by tricyclic antidepressants and NMDA receptor antagonists. ► Our findings are consistent with an upregulation of NMDA receptor function in prion protein null mice.