The Neuroimmunopharmacology of Psychoactive Substances and CNS Drug Discovery
【摘要】：Drug addiction is a serious problem, which causes serious medical and social problems.Currently there is no effective way for treating drug addiction, especially for synthetic drug abuse. Most drug abuse research have been concentrated on neurons in the central nerve system(CNS), however, the action of glia, which accounts for 90% cells in CNS, have been long neglected. We have recently discovered that the psychoactive substances(including opioids, cocaine and methamphetamine) activate microglia. This xenobiotic associated molecular pattern(XAMP)-induced microglia activation occurs through a novel pathway that depends on TLR4. TLR4 activation causes microglia to release pro-inflammatory factors,which modulate the neural circuitry of drug reward and contribute to drug dependence and addiction. Therefore, TLR4 is a good drug discovery target for developing "all-purpose"therapeutics for treating various types of drug addiction. A series of TLR4 antagonists have been discovered by multiple drug discovery strategies for treating drug abuse.