CRF1 receptor-deficiency induces anxiety-like vulnerability to cocaine

Psychopharmacology (Berl). 2014 Oct;231(20):3965-72. doi: 10.1007/s00213-014-3534-1. Epub 2014 Apr 1.


Rationale: 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.

Objectives: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / genetics*
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Central Nervous System Stimulants / pharmacology*
  • Cocaine / pharmacology*
  • Corticotropin-Releasing Hormone / pharmacology
  • Male
  • Mice
  • Mice, Knockout
  • Motor Activity / drug effects*
  • Motor Activity / genetics
  • Receptors, Corticotropin-Releasing Hormone / genetics*
  • Recognition, Psychology / drug effects
  • Recognition, Psychology / physiology


  • Central Nervous System Stimulants
  • Receptors, Corticotropin-Releasing Hormone
  • CRF receptor type 1
  • Corticotropin-Releasing Hormone
  • Cocaine