Disruption of the CRF/CRF1 receptor stress system exacerbates the somatic signs of opiate withdrawal.
Neuron. 2007-02-01; 53(4): 577-589
DOI: 10.1016/j.neuron.2007.01.022
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1. Neuron. 2007 Feb 15;53(4):577-89.
Disruption of the CRF/CRF1 receptor stress system exacerbates the somatic signs
of opiate withdrawal.
Papaleo F(1), Kitchener P, Contarino A.
Author information:
(1)Laboratoire Homéostasie-Allostasie-Pathologie, EA 3666, Université Victor
Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France.
Escape from the extremely stressful opiate withdrawal syndrome may motivate
opiate seeking and taking. The corticotropin-releasing factor receptor-1 (CRF1)
pathway mediates behavioral and endocrine responses to stress. Here, we report
that genetic inactivation (CRF1-/-) as well as pharmacological antagonism of the
CRF/CRF1 receptor pathway increased and prolonged the somatic expression of
opiate withdrawal. Opiate-withdrawn CRF1-/- mice also showed aberrant CRF and
dynorphin expression in the paraventricular nucleus of the hypothalamus (PVN) and
the striatum, indicating profound impairments in stress-responsive brain
circuitry. Intake of nonstressful amounts of corticosterone effectively reduced
the exaggerated somatic reactions of CRF1-/- mice to opiate withdrawal. Exogenous
corticosterone also restored “wild-type-like” patterns of CRF and dynorphin gene
expression in the PVN and the striatum of opiate-withdrawn CRF1-/- mice,
respectively. The present findings unravel a key role for the
hypothalamus-pituitary-adrenal (HPA) system and brain extra-hypothalamic CRF/CRF1
receptor circuitry in somatic, molecular, and endocrine alterations induced by
opiate withdrawal.
DOI: 10.1016/j.neuron.2007.01.022
PMID: 17296558 [Indexed for MEDLINE]