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Project

Glutamate mGluR2 and mGluR5 receptors in addiction: an in vivo multimodal, translational imaging study of their role in deficient corticostriatal control and modulation of dopaminergic neurotransmission.

Addiction is a complex brain disorder leading to a compulsive obsession to use substances despite serious negative consequences. It is one of the most prevalent mental disorders, responsible for 16% of all mortalities and huge treatment costs (> 65 billion € in Europe). The brain’s reward system (with dopamine as important messenger) is dysregulated in addiction, as is the control of the frontal brain cortex over drug-seeking and drug-taking behavior. The molecular processes that underlie vulnerability, craving and relapse risk are poorly understood. Glutamate regulates inhibitory frontal control and aspects of dopaminergic transmission. Central in this process are proteins (receptors) that control glutamate release, especially the presynaptic mGluR2 and postsynaptic mGluR5 receptor. Using two new radioligands to quantify these receptors in the brain (11C-JNJ42491293 developed by us and Janssen Pharmaceutics for mGluR2 and 11C-APB688 for mGluR5), in combination with glutamate MR spectroscopy, this will allow us to study the dysfunction of glutamate transmission in development and relapse of substance addiction (alcohol, nicotine, cocaine, amphetamine), both in humans and in specific novel rodent models. This will be complemented with behavioral correlates, genetics (humans) and microdialysis (rodents). This research aims for an objective diagnostic marker for addiction vulnerability and relapse risks, and potential proof-of-principle for treatment directed at these targets.

Date:1 Jan 2013 →  31 Dec 2016
Keywords:mGluR2, mGluR5, Verslaving
Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences