CRF1 receptor-deficiency induces anxiety-like vulnerability to cocaine.
Psychopharmacology. 2014-04-01; 231(20): 3965-3972
DOI: 10.1007/s00213-014-3534-1
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1. Psychopharmacology (Berl). 2014 Oct;231(20):3965-72. doi:
10.1007/s00213-014-3534-1. Epub 2014 Apr 1.
CRF1 receptor-deficiency induces anxiety-like vulnerability to cocaine.
Morisot N(1), Millan MJ, Contarino A.
Author information:
(1)Univ. Bordeaux, INCIA, UMR 5287, F-33000, Bordeaux, France.
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.
DOI: 10.1007/s00213-014-3534-1
PMID: 24687410 [Indexed for MEDLINE]