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