The corticotropin-releasing factor receptor-2 mediates the motivational effect of opiate withdrawal.

Khalil Rouibi, Angelo Contarino
Neuropharmacology. 2013-10-01; 73: 41-47
DOI: 10.1016/j.neuropharm.2013.05.011

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1. Neuropharmacology. 2013 Oct;73:41-7. doi: 10.1016/j.neuropharm.2013.05.011. Epub
2013 May 21.

The corticotropin-releasing factor receptor-2 mediates the motivational effect of
opiate withdrawal.

Rouibi K(1), Contarino A.

Author information:
(1)Univ. Bordeaux, INCIA, UMR 5287, F-33000 Bordeaux, France.

Altered motivational processes are key features of drug dependence and
withdrawal, yet their neural mechanisms remain largely unknown. The present study
shows that genetic disruption of the corticotropin-releasing factor receptor-2
(CRF₂-/-) does not impair motivation for palatable food in drug-naïve mice.
However, CRF₂ receptor-deficiency effectively reduces the increase in palatable
food-driven motivation induced by opiate withdrawal. Indeed, both in male and
female wild-type mice, withdrawal from escalating morphine doses (20-100 mg/kg)
induces a dramatic and relatively long-lasting (6 days) increase in palatable
food-driven operant behavior under a progressive ratio (PR) schedule of
reinforcement. In contrast, either male or female morphine-withdrawn CRF₂-/- mice
show smaller and shorter (2 days) increases in motivation than wild-type mice.
Nevertheless, CRF₂ receptor-deficiency does not impair the ability to
discriminate reinforced behavior prior to, during the partial opiate withdrawal
periods occurring between morphine injections and following drug discontinuation,
indicating preserved cognitive function. Moreover, CRF₂ receptor-deficiency does
not affect the ambulatory or body weight effects of intermittent morphine
injections and withdrawal. These results provide initial evidence of a
gender-independent and specific role for the CRF₂ receptor in the motivational
effects of opiate withdrawal.

Copyright © 2013 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.neuropharm.2013.05.011
PMID: 23707482 [Indexed for MEDLINE]

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