The CRF1 and the CRF2 receptor mediate recognition memory deficits and vulnerability induced by opiate withdrawal.
Neuropharmacology. 2016-06-01; 105: 500-507
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1. Neuropharmacology. 2016 Jun;105:500-507. doi: 10.1016/j.neuropharm.2016.02.021.
Epub 2016 Feb 18.
The CRF1 and the CRF2 receptor mediate recognition memory deficits and
vulnerability induced by opiate withdrawal.
Morisot N(1), Contarino A(2).
(1)Univ. Bordeaux, INCIA, UMR 5287, 33000 Bordeaux, France; CNRS, INCIA, UMR
5287, 33000 Bordeaux, France.
(2)Univ. Bordeaux, INCIA, UMR 5287, 33000 Bordeaux, France; CNRS, INCIA, UMR
5287, 33000 Bordeaux, France. Electronic address: .
Opiate use disorders are associated with impaired cognitive function and altered
stress-responsive systems. The corticotropin-releasing factor (CRF) system
mediates stress responses via CRF1 and CRF2 receptors and may be implicated in
substance use disorders. However, the specific role for each of the two known CRF
receptor subtypes in cognitive impairment induced by opiate administration and
withdrawal remains to be elucidated. In the present study, CRF1-/-, CRF2-/- and
their respective wild-type mice are injected with escalating doses of morphine
and cognitive function assessed by the novel object recognition (NOR) memory task
throughout relatively long periods of opiate withdrawal. Early (2 days) phases of
opiate withdrawal impair NOR memory in wild-type, CRF1-/- and CRF2-/- mice.
However, the duration of opiate withdrawal-induced NOR memory deficits is
prolonged in CRF1-/- but shortened in CRF2-/- mice, as compared to their
respective wild-type mice, indicating opposite roles for the two CRF receptor
subtypes. Nevertheless, following apparent recovery, exposure to an environmental
stressor induces the reemergence of NOR memory deficits in long-term
opiate-withdrawn wild-type but not CRF1-/- or CRF2-/- mice, indicating an
essential role for both CRF receptor subtypes in stress vulnerability. These
findings bring initial evidence of a complex physiopathological role for the CRF
system in cognitive deficits and the long-lasting vulnerability induced by opiate
Copyright © 2016 Elsevier Ltd. All rights reserved.
PMID: 26907806 [Indexed for MEDLINE]