Cycle 3 project 4

 Molecular basis of vulnerability to addiction


PhD student: Yongmei Sun, China
Home Institute: Amsterdam Neuroscience; Principle Investigator: Sabine Spijker
Host Institute: Bordeaux Neurocampus; Principle Investigator: Pier-Vincenzo Piazza / Véronique Deroche-Gamonet

Executive Summary

Drug addiction causes severe health problems and has substantial socio-economic impact. Unfortunately, its treatment is hampered by high relapse rates even after months of abstinence. A major cause for relapse is the exposure to stimuli, both contextual and discrete, that over time become associated with the rewarding substance. Such stimuli evoke memories of the rewarding effects, induce craving and precipitate relapse. Successful treatment strategies for human drug addiction crucially relies on the identification of molecular mechanisms involved using a model with high face-validity; i.e., the Addict and non-Addict rat model, that captures three of the essential diagnostic criteria (DSM-IV criteria) of addiction. In this project, we aim to disentangle the complex molecular and cellular cascades that are underlying the vulnerability trait that leads to uncontrollable drug seeking.

This project aims specifically at revealing the biological basis of transition to addiction, using individual rats that show the DSM-IV criteria of addiction, i.e., a trait that develops only in a small proportion of rats that have sustained cocaine self-administration. Focusing on two central brain regions crucial to drug escalation and relapse to drug-seeking, the nucleus accumbens (NAc) and the prefrontal cortx (PFC), we will analyze drug-prone induced adaptations at the subcellular level, i.e., at the level of the synaptic proteome. In addition, dynamic networks of protein complexes will be analyzed for these drug-prone proteins to reveal the temporal aspects of the transition to addiction. This focus on the synapse is important as adaptations in synaptic protein levels are more likely to have a functional consequence. Based on these findings, intervention tools will be generated to show the causal relation of drug-prone induced adaptations in the escalation to addiction.

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