title: CRF1 receptor-deficiency induces anxiety-like vulnerability to cocaine.
abstract: BACKGROUND
  The intake of psychostimulant drugs may induce cognitive dysfunction and negative affective-like states, and is associated with increased activity of stress-responsive systems. The corticotropin-releasing factor (CRF) system mediates neuroendocrine, behavioural and autonomic responses to stressors, and might be implicated in substance-related disorders. CRF signalling is mediated by two receptor types, named CRF1 and CRF2.
  
  
  OBJECTIVE
  The present study aims to elucidate the role for the CRF1 receptor in cognitive dysfunction and anxiety-like states induced by cocaine.
  
  
  RESULTS
  The genetic inactivation of the CRF1 receptor (CRF1+/- and CRF1-/-) does not influence recognition memory in drug-naïve mice, as assessed by the novel object recognition (NOR) test. Moreover, the chronic administration of escalating doses of cocaine (5-20 mg/kg, i.p.) induces NOR deficits, which are unaffected by CRF1 receptor-deficiency. However, the same drug regimen reveals an anxiety-like vulnerability to cocaine in CRF1-/- but not in wild-type or CRF1+/- mice, as assessed by the elevated plus maze test.
  
  
  CONCLUSIONS
  The present findings indicate dissociation of cognitive dysfunction and anxiety-like states induced by cocaine. Moreover, they unravel a novel mechanism of vulnerability to psychostimulant drugs.
authors.affiliation: Univ. Bordeaux, INCIA, UMR 5287, F-33000, Bordeaux, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Morisot
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Millan
authors.forename: Angelo
authors.initials: A
authors.lastname: Contarino
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects* / Q000235:genetics; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D000099052:CRF Receptor, Type 1
chemical_list: D000697:Central Nervous System Stimulants; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D003042:Cocaine