CRF₂ receptor-deficiency reduces recognition memory deficits and vulnerability to stress induced by cocaine withdrawal.
Int. J. Neuropsychopharm.. 2014-05-06; 17(12): 1969-1979
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1. Int J Neuropsychopharmacol. 2014 Dec;17(12):1969-79. doi:
10.1017/S1461145714000625. Epub 2014 May 6.
CRF₂ receptor-deficiency reduces recognition memory deficits and vulnerability to
stress induced by cocaine withdrawal.
Morisot N(1), Le Moine C(1), Millan MJ(2), Contarino A(1).
(1)University of Bordeaux,INCIA, UMR 5287, Bordeaux,France.
(2)URDN, Institut de Recherches Servier,Croissy-sur-Seine,France.
Psychostimulant drug abuse, dependence and withdrawal are associated with
cognitive dysfunction and impact stress-sensitive systems. The
corticotropin-releasing factor (CRF) system orchestrates stress responses via
CRF1 and CRF2 receptors and is implicated in substance use disorders. However,
CRF2 role in psychostimulant drug-induced cognitive dysfunction remains to be
elucidated. In the present study, wild-type and CRF2-/- mice are injected with
cocaine and memory assessed by the novel object recognition (NOR) task throughout
relatively long periods of drug withdrawal. Following recovery from the
drug-induced memory deficits, the mice are stressed prior to the NOR task and
brain gene expression evaluated by in situ hybridization. Cocaine impairs NOR
memory in wild-type and CRF2-/- mice. However, following cocaine withdrawal NOR
memory deficits last less time in CRF2-/- than in wild-type mice. Furthermore, a
relatively mild stressor induces the re-emergence of NOR deficits in long-term
cocaine-withdrawn wild-type but not CRF2-/- mice. Cocaine-withdrawn mice show a
genotype-independent higher c-fos expression in the NOR memory-relevant
perirhinal cortex than drug-naïve mice. However neither genotype nor drug
withdrawal affect the expression of tyrosine hydroxylase in the ventral tegmental
area or the locus coeruleus and CRF in the central nucleus of the amygdala or the
paraventricular nucleus of the hypothalamus, brain regions implicated in stress
and drug responses. These data indicate a new role for the CRF2 receptor in
cognitive deficits induced by cocaine withdrawal, both as regards to their
duration and their re-induction by stress. Interestingly, prototypical brain
stress systems other than CRF do not appear to be involved.
PMID: 24800964 [Indexed for MEDLINE]