CRF1 receptor-deficiency induces anxiety-like vulnerability to cocaine.

Abstract:

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.

journal_title

Psychopharmacology

authors

Morisot N,Millan MJ,Contarino A

doi

10.1007/s00213-014-3534-1

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

3965-72

issue

20

eissn

0033-3158

issn

1432-2072

journal_volume

231

pub_type

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