Mechanisms of Psychostimulant-Induced Structural Plasticity

Psychostimulants robustly induce alterations in neuronal structural plasticity throughout brain reward circuits. However, despite our extensive understanding of how these circuits modulate motivated behavior, it is still unclear whether structural plasticity within these regions drives pathological behavioral responses in addiction. Although these structural changes have been subjected to an exhaustive phenomenological characterization, we still have a limited understanding of the molecular mechanisms regulating their induction and the functional relevance of such changes in mediating addiction-like behavior. Herewe have highlighted the known molecular pathways and intracellular signaling cascades that regulate psychostimulant-induced changes in neuronal morphology and synaptic restructur-ing, and we discuss them in the larger context of addiction behavior. Addiction is characterized by persistent drug-seeking behavior and a high frequency of relapse. The repercussions of such drug seeking and relapse behavior place a strong economic, social, and health burden on all levels of soci-ety. In fact, the World Drug Report estimates that 5 % of the world’s population use illicit drugs, placing a suggested socioeconomic bur-den of several hundred billion U.S. dollars an-nually (UNODC 2010). Unfortunately, there are still relatively few effective therapeutic in-terventions available for the treatment of sub-stance abuse. This has led to a concerted effort to reveal the molecular and cellular basis o