Introduction 3. Opioid receptor signaling 3.1. Receptor phosphorylation by protein kinase C 3.2. Modulation of receptor internalization by protein kinase C 3.3. PKC hypothesis for morphine tolerance/desensitization 3.4. Heterologous regulation of opioid receptor endocytosis 4. Plasticity in neuronal networks 4.1. Anti-opioid glutamate-NMDA receptor system 4.2. BDNF system that supports the anti-opioid NMDA receptor system 4.3. Other systems that support the anti-opioid NMDA receptor system 4.4. Anti-opioid neuropeptide systems 4.5 Opioid-induced hyperalgesia by neuropeptides 4.6 Glial cell involvements in the anti-opioid system 5. Conclusion