NeuropsychopharmARCology: Shaping Neuroplasticity through Arc/ Arg3.1 Modulation

Activity-regulated cytoskeleton-associated protein (aka activity-regulated gene Arg3.1) belongs to the effector gene family of the immediate early genes. This family encodes effector proteins, which act directly on cellular homeostasis and function. Arc/Arg3.1 is localized at dendritic processes, allowing the protein local synthesis on demand, and it is considered a reliable index of activity- dependent synaptic changes. Evidence also exists showing the critical role of Arc/Arg3.1 in memory processes. The high sensitivity to changes in neuronal activity, its specific localization as well as its involvement in long-term synaptic plasticity indeed make this effector gene a potential, critical target of the action of psychotropic drugs. In this review, we focus on antipsychotic and antidepressant drugs as well as on psychostimulants, which belong to the category of drugs of abuse but can also be used as drugs for specific disorders of the central nervous system (i.e., Attention Deficit Hyperactivity Disorder). It is demonstrated that psychotropic drugs with different mechanisms of action converge on Arc/Arg3.1, providing a means whereby Arc/Arg3.1 synaptic modulation may contribute to their therapeutic activity. The potential translational implications for different neuropsychiatric conditions are also discussed, recognizing that the treatment of these disorders is indeed complex and involves the simultaneous regulation of several dysfunctional mechanisms.