Increased training compensates for OX1R blockage-impairment of spatial memory and c-Fos expression in different cortical and subcortical areas.

•Blocking OX1R impairs spatial learning in MWM in a training-dependent manner.•Strong vs weak training in a spatial task increases HPC-thalamic-cortical activity.•SB-334867 diminishes c-Fos expression in areas with a high density of OX1R.•Training compensates for SB-334867 impairing effects on MWM and c-Fos expression.•Activation of DG, gRSC, PL and CL could prevent impairment of MWM by SB-334867.