Multimodal Neuroimaging x Optogenetics: A Novel Approach to Study Reward Processing Under Pathological Conditions

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Background: Midbrain dopamine neurons play a key role in reward processing and subsequent goaldirected behaviour. Altered dopaminergic activity and dysfunctional reward processing occurs in several psychiatric disorders. Especially in drug addiction goal-directed behaviour is severely impaired, as the behavioural activities of a drug addict become increasingly drug-oriented at the expense of all other daily activities. The underlying neurobiology of altered reward processing during the development, maintenance, and possible remission of an addicted behaviour is poorly understood. Goa/s.'To study the dynamics of midbrain dopamine neurons and their connectivity within the reward system by multimodal 9.4T magnetic resonance imaging (MRI) in rats that show addictive-like behaviour. Following a prolonged period of intravenous cocaine self-administration approx. 15% of rats develop addictive-like behaviour similar to that seen in human cocaine users diagnosed as addicts. Using this animal model, alterations in reward processing and underlying dopaminergic activity and connectivity will be studied longitudinally by means of repeated multimodal MRI in animals that become addicted versus animals that show resilience to addictive behaviour.Outcome.'These studies will provide fundamental new insights into reward processing and underlyingalterations in dopaminergic function and connectivity in the context of addictive behaviour. Given thatoutcome measures from experimental animals will be derived from neuroimaging studies the findingswill be directly translatable to the human condition and will dramatically impact on our knowledge ofdrug addiction, pathological gambling, depression, and several other psychiatric disorders.