Mu opioid receptors (MORs) mediate the strong analgesic and rewarding effects of morphine. We used non-invasive imaging fMRI in wild-type and MOR knockout mice to assess MOR-dependent effects at the scale of the whole brain. Here, we present striatum seed-based signatures identified by BOLD activation map, functional connectivity and directionality. We identified MOR-specific activation of the striatum between 2 and 7 minutes after morphine administration. Furthermore, during this time interval, the brain connectivity was altered by morphine in wild type but not mutant mice. This is the first reported on-target morphine activation signature in the striatum of live animals.