CRF2 receptor-deficiency eliminates opiate withdrawal distress without impairing stress coping.
Mol Psychiatry. 2011-09-27; 17(12): 1283-1294
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1. Mol Psychiatry. 2012 Dec;17(12):1283-94. doi: 10.1038/mp.2011.119. Epub 2011 Sep
CRF2 receptor-deficiency eliminates opiate withdrawal distress without impairing
Ingallinesi M(1), Rouibi K, Le Moine C, Papaleo F, Contarino A.
(1)Unité de Nutrition et Neurosciences, Université de Bordeaux, Bordeaux, France.
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.
PMID: 21946917 [Indexed for MEDLINE]