CRF2 receptor-deficiency eliminates opiate withdrawal distress without impairing stress-coping

Angelo Contarino (1) , Manuela Ingallinesi (1) , Khalil Rouibi (1) , Catherine Le Moine (1) , Francesco Papaleo (1)

1 INCIA - Institut de Neurosciences cognitives et intégratives d'Aquitaine

The opiate withdrawal syndrome is a severe stressor that powerfully triggers addictive drug intake. However, no treatment yet exists that effectively relieve opiate withdrawal distress and spares stress-coping abilities. The corticotropin-releasing factor (CRF) system mediates the stress response but its role in opiate withdrawal distress and bodily strategies aimed to cope with is unknown. CRF-like signaling is transmitted by two receptor pathways, termed CRF1 and CRF2. Here, we report that CRF2 receptor-deficient (CRF2-/-) mice lack the dysphoria-like and the anhedonia-like states of opiate withdrawal. Moreover, in CRF2-/- mice opiate withdrawal does not increase the activity of brain dynorphin (DYN), CRF and periaqueductal gray (PAG) circuitry, which are major substrates of opiate withdrawal distress. Nevertheless, CRF2 receptor-deficiency does not impair brain, neuroendocrine and autonomic stress-coping responses to opiate withdrawal. The present findings point to the CRF2 receptor pathway as a unique target to relieve opiate withdrawal distress without impairing stress-coping abilities.

Mots clés: opiate withdrawal distress; negative affect; stress-coping; corticotropin-releasing factor (CRF); CRF2 receptor pathway

Domaines: Psychiatrie et santé mentale

Angelo Contarino, Manuela Ingallinesi, Khalil Rouibi, Catherine Le Moine, Francesco Papaleo. CRF2 receptor-deficiency eliminates opiate withdrawal distress without impairing stress-coping. Molecular Psychiatry, 2011, ⟨10.1038/mp.2011.119⟩. ⟨hal-00682812⟩