title: CRF2 receptor-deficiency eliminates opiate withdrawal distress without impairing stress coping.
abstract: The opiate withdrawal syndrome is a severe stressor that powerfully triggers addictive drug intake. However, no treatment yet exists that effectively relieves 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 CRF(1) and CRF(2). Here, we report that CRF(2) receptor-deficient (CRF(2)(-/-)) mice lack the dysphoria-like and the anhedonia-like states of opiate withdrawal. Moreover, in CRF(2)(-/-) mice opiate withdrawal does not increase the activity of brain dynorphin, CRF and periaqueductal gray circuitry, which are major substrates of opiate withdrawal distress. Nevertheless, CRF(2) receptor-deficiency does not impair brain, neuroendocrine and autonomic stress-coping responses to opiate withdrawal. The present findings point to the CRF(2) receptor pathway as a unique target to relieve opiate withdrawal distress without impairing stress-coping abilities.
authors.affiliation: Unité de Nutrition et Neurosciences, Université de Bordeaux, Bordeaux, France.
authors.forename: M
authors.initials: M
authors.lastname: Ingallinesi
authors.forename: K
authors.initials: K
authors.lastname: Rouibi
authors.forename: C
authors.initials: C
authors.lastname: Le Moine
authors.forename: F
authors.initials: F
authors.lastname: Papaleo
authors.forename: A
authors.initials: A
authors.lastname: Contarino
mesh_terms: D000223:Adaptation, Psychological; D000818:Animals; D016739:Behavior, Addictive / Q000235:genetics* / Q000523:psychology*; D001921:Brain / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis; D004195:Disease Models, Animal; D004399:Dynorphins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009293:Opioid-Related Disorders / Q000150:complications / Q000235:genetics / Q000523:psychology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D013315:Stress, Psychological / Q000150:complications / Q000235:genetics* / Q000523:psychology; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000523:psychology*; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
chemical_list: C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D004399:Dynorphins; D003346:Corticotropin-Releasing Hormone; D014446:Tyrosine 3-Monooxygenase; D003345:Corticosterone