Given that inhibition of nNOS attenuates the development of persistent pain and morphine analgesic tolerance and physical dependence [34,35], it is very likely that the dissociation of NMDARs from NO signaling caused by PSD-93 deletion is also involved in the mechanism underlying impairing persistent pain and morphine analgesic tolerance and physical dependence in the KO mice. The gene discussed is NOS1; the disease is substance dependence.