Since ketamine has been found to act antidepressant, NMDA receptor antagonists are investigated regarding their potential use in therapy of depression. In this study we investigated the effects of traxoprodil and lanicemine on resting state functional connectivity in the rat brain. Both drugs significantly altered hippocampal-prefrontal (Hc-PFC) connectivity with more pronounced effect of traxoprodil. Interestingly the pronounced effects on intra PFC connectivity found in a previous ketamine study could not be observed. Traxoprodil also reduced whole brain network segregation. HC-PFC connectivity appears to be a promising target for further investigation of NMDA receptor antagonists and their antidepressant effects.