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HDR – Angelo Contarino

13 June 2012

Role of the corticotropin-releasing factor system in the opiate withdrawal syndrome


Opiate dependence is a chronic, relapsing disorder with a major impact on public health. The extremely stressful signs and symptoms of the opiate withdrawal syndrome are key clinical features of opiate dependence that might strongly contribute to impulsive/compulsive drug-seeking and loss of control upon drug-taking. The CRF system coordinates behavioral and neuroendocrine responses to stressors. Using clinically-relevant experimental mouse models, our former research activity provides initial evidence of a critical, but differential, role for each of the two known CRF receptor pathways, CRF1 and CRF2, in the opiate withdrawal syndrome. Indeed, genetic inactivation of CRF1 receptors eliminates dysphoria-like states but dramatically worsen the somatic signs and the ability to cope with the stress of opiate withdrawal.
In contrast, genetic inactivation of CRF2 receptors eliminates dysphoria-like, anhedonia-like and somatic signs of opiate withdrawal without impairing stress coping. Furthermore, CRF2 receptor-deficiency effectively reduces the motivational disorders (increases) associated with opiate intake and withdrawal in either male or female mice.

Using clinically-relevant experimental mouse models, our future research activity aims at elucidating the specific role for the CRF1 and the CRF2 receptor pathway also in brain reward systems dysfunction, cognitive deficits and social breakdown that are often associated with opiate dependence and withdrawal, and the long-lasting vulnerability following cessation of drug intake. Moreover, molecular biology studies will be carried out in order to dissect the relative role for the CRF1 and the CRF2 receptor pathway, and other stress-responsive systems, in the neural mechanisms underlying drug dependence and withdrawal. The findings of our studies might help identify the role for the CRF and other major stress-responsive systems in key clinical features of the opiate withdrawal syndrome. Thus, a better understanding of the physiopathological mechanisms underlying the myriad of signs and symptoms of the opiate withdrawal syndrome might open the way to new research-based pre-clinical and clinical trials aimed at developing novel and effective treatments for drug (opiate) dependence.

Keywords: Drug dependence; Opiate withdrawal syndrome; Stress; CRF system; CRF receptor signaling pathways; Therapy

Angelo Contarino

Maître de conférence – PhD, Université Bordeaux 2 , Chercheur, CNRS UMR 5287 – INCIA Institut de Neurosciences cognitives et intégratives d’Aquitaine. Equipe Neuropsychopharmacologie de l’addiction. Team leader: Martine Cador

Parcours scientifique

Angelo Contarino obtient un premier doctorat en médecine en 1992 et un second en pharmacologie en 1996 à l’Université de Padoue, sur le sujet de thèse «Sensitization to the rewarding effects of opiate drugs». Il effectue son stage postdoctoral de 1997 à 2000 au «Scripps Research Institute» de La Jolla, en Californie, sous la direction de Lisa Gold et de George Koob. En 2004 obtient un poste de Maitre de Conférences à l’Université Victor Segalen Bordeaux 2 pour intégrer finalement en Janvier 2011 l’équipe de Martine Cador «Neuropsychopharmacologie de l’addiction» à l’Institut de Neurosciences Cognitives et Intégratives d’Aquitaine (INCIA), Université de Bordeaux et UMR CNRS 5287.

Angelo Contarino est aussi à l’initiative du Symposium annuel «Nutrition & Neurosciences» qui se déroule chaque année à l’Institut Magendie.

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13 June 2012
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