Compulsive disorders, including drug abuse and compulsive overeating, represent prevalent neuropsychiatric diseases that have a large health and socio-economic impact in the European population.

These disorders are produced by an alteration of the capability to control seeking for reward and seem linked by common neurobiological substrates. However, there is an important gap in the availability of reliable behavioural models in animals that permit to investigate compulsion towards reward in the perspective of human pathologies

The present proposal will use new sophisticated behavioural and neuroimaging techniques for the characterisation of four new and complementary animal models of compulsive disorders, allowing to precisely analyse the main components of those behavioural alterations. The study will be performed in mice and rats, including the transfer of rat models to mice when necessary.

The behavioural and molecular charac-terisation of the models, along withparallel neuroimaging (PET), will provide a complete anatomical and functional illustration of the reward pathways imbalance in the above-mentioned pathological situations. Novel behavioural paradigms will be proposed, tested and validated within the project taking advantage from cuttingedge imaging technologies. Molecular studies will characterise changes induced in several key elements of the reward circuits during these behavioural disorders. After the full characterisation of the models, they will be used on genetically modified mice for glucocorticoid receptors to ascertain correlations between behavioural and genetic components of compulsion in drug addiction and eating disorders.

Hence, reliable and predictive animal models will be fully characterised and employed to better understand the mechanisms involved in those alterations and to design new therapeutic strategies in neuropsychiatric disorders related to compulsive behaviour.

1. Deliver four phenotypically well-characterised animal models, namely, the modified conflict, the deprivation and the reinstatement models of compulsive drug intake, and the compulsive food seeking/taking model, addressing different components of compulsion using rats and mice.
2. Elucidate the role of selected gene activities and protein receptors in the neurobiological mechanisms involved in compulsive disorders.
3. Provide complete new structural and functional illustration of the reward pathways imbalance found in compulsion using cutting-edge imaging techniques (PET).

In this context, PHECOMP is an innovative project as it will study neuro-psychiatric disorders related to compulsive behaviour focussing on food overeating and drug consumption using, not only sophisticated behavioural and molecular approaches, but also with parallel new neuroimaging technologies.

This will allow delivering four new animal models fully characterised and ready to be used by the scientific community, as well as to propose new molecular markers of food and drug-related compulsive behaviours as new targets for the pharmaceutical industry.