Beyond Neurotransmission: Exploring Roles for Synaptic Dopaminylation in Drug-induced Plasticity
Substance use disorder is a chronic, relapsing illness that affects millions of individuals worldwide; however, few effective treatment options for substance abuse and addiction exist. Here, employing a unique combination of biochemical, molecular and behavioral approaches, we examine a highly novel role for the neurotransmitter dopamine in the direct regulation of protein function at reward circuitry synapses, processes that likely contribute to addictive behaviors. This pilot proposal therefore aims to transformatively integrate expertise from multiple disciplines (e.g., chromatin biochemistry, neuroepigenetics and behavioral neuroscience) to begin characterizing so-called protein “dopaminylation” in the central nervous system, as well as to elucidate its potential role in compulsive cocaine seeking. The overarching goal of this work is thus to identify novel molecular underpinnings of life-long addiction that will allow for the development of more effective therapeutic interventions.