Mediating the effects of drug abuse: The role of Narp in synaptic plasticity

Abstract

There has been remarkable progress in deciphering the mo-lecular mechanisms that mediate synaptic plasticity. Ad-vances have stimulated interest in determining whether these plasticity mechanisms also mediate the long-lasting behavioral effects induced by drugs of abuse. The observa-tion that drugs of abuse, such as cocaine or morphine, can elicit robust immediate early gene (IEG) responses similar to those induced by long-term potentiation stimulation has provided important support for this hypothesis. Evidence that repeated administration of cocaine produces altera-tions in expression and trafficking of AMPA receptors, pro-cesses that play a central role in synaptic plasticity, has also bolstered this view. Neuronal activity-regulated pentraxin (Narp), an IEG, has emerged as an attractive candidate to mediate long-term effects of drugs of abuse because it en-codes a secreted protein that binds to the extracellular sur-face of AMPA receptors and regulates their trafficking. In this review we provide background information on Narp and closely related proteins, the neuronal pentraxins, and summarize studies of Narp knockout mice demonstrating that this IEG modulates long-term behavioral responses to drugs of abuse.