Tolerance, physical dependence, and addiction caused by chronic treatment with narcotics are important models in the study of basic neuronal plasticity. In our work, we have identified several critical molecules and pathways that are relevant to the development of peripheral and central tolerance and addiction (J.Neurosci. 2000; J. Pharmacol. Exp. Ther. 2000; Neurosci Lett. 1997) Further, we identified new technology for the use of electroporation of specific genes into selected knockout loci in mouse brains. This resulted in identification of the locus-specific role of the anti-opioid system by NMDA, and the nociception/orphanin FQ receptor signaling in development of opioid addiction (J.Neurosci. 2000, 2003).