title: CRF1receptor-deficiency increases cocaine reward.
abstract: 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 CRF1receptor-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 CRF1receptor-deficiency alters the rewarding effects of cocaine. Acute pharmacological antagonism of the CRF1receptor 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 CRF1receptor-dependent cocaine reward but induces stereotypy responses to cocaine. These results indicate a critical role for the CRF1receptor in cocaine reward, independently of the closely related HPA axis activity.
authors.affiliation: CNRS, INCIA, UMR 5287, 33000 Bordeaux, France; Univ. Bordeaux, 33000 Bordeaux, France. Electronic address: angelo.contarino@u-bordeaux.fr.
authors.forename: Angelo
authors.initials: A
authors.lastname: Contarino
authors.affiliation: INSERM U1215, NeuroCentre Magendie, 33077 Bordeaux, France; Univ. Bordeaux, 33000 Bordeaux, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Kitchener
authors.affiliation: INSERM U1215, NeuroCentre Magendie, 33077 Bordeaux, France; Univ. Bordeaux, 33000 Bordeaux, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Vallée
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, via Morego, 30, 16163 Genova, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Papaleo
authors.affiliation: INSERM U1215, NeuroCentre Magendie, 33077 Bordeaux, France; Univ. Bordeaux, 33000 Bordeaux, France.
authors.forename: Pier-Vincenzo
authors.initials: PV
authors.lastname: Piazza
mesh_terms: D000818:Animals; D002940:Circadian Rhythm; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012201:Reward; D013239:Stereotyped Behavior / Q000187:drug effects; D000099052:CRF Receptor, Type 1
chemical_list: D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D011965:Receptors, Glucocorticoid; C103016:antalarmin; D000099052:CRF Receptor, Type 1; D003042:Cocaine; D003345:Corticosterone
keywords: Cocaine; Corticotropin-releasing factor (CRF) receptor 1; Hypothalamus-pituitary-adrenal (HPA) axis; Reward; Stereotypy