The Substantia Nigra Pars Reticulata in Sedative-Hypnotic Withdrawal

Abstract Sedative-hypnotic drugs including alcohol, benzodiazepines, and barbiturates, are widely used and abused for their euphoric and sedative properties. Sedative-hypnotic abuse and addiction is a complex, heterogeneous disorder, with biological (genetic) factors strongly influencing risk for dependence. Physiological dependence and associated withdrawal are thought to be a powerful motivational force that perpetuates sedative-hypnotic use/abuse, and enhances vulnerability to relapse. Recently, the substantia nigra pars reticulata (SNr) has been identified as crucially involved in sedative-hypnotic withdrawal symptoms (e.g., convulsions). The Mpdz gene has been implicated in sedative-hypnotic physiological dependence and associated withdrawal episodes in mice, with Mpdz expression within the caudolateral subregion of the SNr crucially involved.