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CRF1 receptor-deficiency induces anxiety-like vulnerability to cocaine

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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.

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Acknowledgements

This study is supported by the Institut de Recherche Servier (IDRS), the Université de Bordeaux and the Centre National de la Recherche Scientifique (CNRS). Funding sources have no involvement in the conduct of the research and/or preparation of the article. The authors wish to thank Anne Fayoux and Stéphane Lelgouach for valuable assistance with animal care. All authors declare that they have no conflicts of interest.

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Correspondence to Angelo Contarino.

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Morisot, N., Millan, M.J. & Contarino, A. CRF1 receptor-deficiency induces anxiety-like vulnerability to cocaine. Psychopharmacology 231, 3965–3972 (2014). https://doi.org/10.1007/s00213-014-3534-1

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