Interference Peptides: a Novel Therapeutic Approach Targeting Synaptic Plasticity in Drug Addiction

Synaptic plasticity at excitatory synapses has been proposed as the cellular substrate of information processing and memory formation in the brain under both physiological and pathological conditions, including addiction. There is a growing body of evidence that implicates long-term depression (LTD), particularly in the nucleus accumbens (NAc), as a potential mediator of drug-induced neural plasticity. In animals, behavioral sensitization is used to model enduring changes in neuronal activity and behavior that result from repeated exposure to drugs of abuse. Given the links between behavioral sensitization and enduring drug-induced neuroplasticity, it is possible that compounds that can disrupt LTD may form the basis for a rational drug development strategy for repairing abnormal synaptic functions that are related to exposure to addictive substances. The data reviewed here provide evidence that facilitated AMPAR endocytosis and LTD in the NAc is critically involved in behavioral sensitization associated with drug addiction, indicating that both the expression and possibly the induction phases of LTD may represent promising targets for developing novel therapeutics for the clinical management of drug addicts.