CRF1 receptor-deficiency increases cocaine reward.
Neuropharmacology. 2017-05-01; 117: 41-48
DOI: 10.1016/j.neuropharm.2017.01.024
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1. Neuropharmacology. 2017 May 1;117:41-48. doi: 10.1016/j.neuropharm.2017.01.024.
Epub 2017 Jan 27.
CRF1 receptor-deficiency increases cocaine reward.
Contarino A(1), Kitchener P(2), Vallée M(2), Papaleo F(3), Piazza PV(2).
Author information:
(1)CNRS, INCIA, UMR 5287, 33000 Bordeaux, France; Univ. Bordeaux, 33000 Bordeaux,
France. Electronic address: .
(2)INSERM U1215, NeuroCentre Magendie, 33077 Bordeaux, France; Univ. Bordeaux,
33000 Bordeaux, France.
(3)Department of Neuroscience and Brain Technologies, Istituto Italiano di
Tecnologia, via Morego, 30, 16163 Genova, Italy.
Stimulant drugs produce reward but also activate stress-responsive systems. The
corticotropin-releasing factor (CRF) and the related
hypothalamus-pituitary-adrenal (HPA) axis stress-responsive systems are activated
by stimulant drugs. However, their role in stimulant drug-induced reward remains
poorly understood. Herein, we report that CRF1 receptor-deficient (CRF1-/-), but
not wild-type, mice show conditioned place preference (CPP) responses to a
relatively low cocaine dose (5 mg/kg, i.p.). Conversely, wild-type, but not
CRF1-/-, mice display CPP responses to a relatively high cocaine dose (20 mg/kg,
i.p.), indicating that CRF1 receptor-deficiency alters the rewarding effects of
cocaine. Acute pharmacological antagonism of the CRF1 receptor by antalarmin also
eliminates cocaine reward. Nevertheless, CRF1-/- mice display higher stereotypy
responses to cocaine than wild-type mice. Despite the very low plasma
corticosterone concentration, CRF1-/- mice show higher nuclear glucocorticoid
receptor (GR) levels in the brain region of the hippocampus than wild-type mice.
Full rescue of wild-type-like corticosterone and GR circadian rhythm and level in
CRF1-/- mice by exogenous corticosterone does not affect CRF1 receptor-dependent
cocaine reward but induces stereotypy responses to cocaine. These results
indicate a critical role for the CRF1 receptor in cocaine reward, independently
of the closely related HPA axis activity.
Copyright © 2017 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.neuropharm.2017.01.024
PMID: 28137450 [Indexed for MEDLINE]