PMID- 26860616
OWN - NLM
STAT- MEDLINE
DCOM- 20180424
LR  - 20180424
IS  - 1369-1600 (Electronic)
IS  - 1355-6215 (Linking)
VI  - 22
IP  - 4
DP  - 2017 Jul
TI  - Alcohol withdrawal induces long-lasting spatial working memory impairments: 
      relationship with changes in corticosterone response in the prefrontal cortex.
PG  - 898-910
LID - 10.1111/adb.12371 [doi]
AB  - This study intends to determine whether long-lasting glucocorticoids (GCs) 
      dysregulation in the prefrontal cortex (PFC) or the dorsal hippocampus (dHPC) 
      play a causal role in the maintenance of working memory (WM) deficits observed 
      after alcohol withdrawal. Here, we report that C57/BL6 male mice submitted to 
      6 months alcohol consumption (12 percent v/v) followed by 1 (1W) or 6 weeks (6W) 
      withdrawal periods exhibit WM deficits in a spatial alternation task and an 
      exaggerated corticosterone rise during and after memory testing in the PFC but 
      not the dHPC. In contrast, emotional reactivity evaluated in a plus-maze is 
      altered only in the 1W group. No behavioral alterations are observed in mice 
      still drinking alcohol. To determine the causal role of corticosterone in the 
      withdrawal-associated long-lasting WM deficits, we further show that a single 
      intraperitoneal injection injection of metyrapone (an inhibitor of corticosterone 
      synthesis) 30 minutes before testing, prevents withdrawal-associated WM deficits 
      and reestablishes PFC activity, as assessed by increased phosphorylated C-AMP 
      Response Element-binding protein (CREB) immunoreactivity in withdrawn mice. 
      Finally, we show that intra-PFC blockade of mineralocorticoid receptors by 
      infusion of spironolactone and, to a lesser extent, of GCs receptors by injection 
      of mifepristone reverses the WM deficits induced by withdrawal whereas the same 
      injections into the dHPC do not. Overall, our study evidences that long-lasting 
      GCs dysfunction selectively in the PFC is responsible for the emergence and 
      maintenance of WM impairments after withdrawal and that blocking prefrontal 
      mineralocorticoid receptors receptors restores WM in withdrawn animals.
CI  - (c) 2016 Society for the Study of Addiction.
FAU - Dominguez, Gaelle
AU  - Dominguez G
AD  - Universite de Bordeaux, INCIA CNRS UMR 5287, France.
AD  - Universite Francois Rabelais, Inserm U930, France.
FAU - Belzung, Catherine
AU  - Belzung C
AD  - Universite Francois Rabelais, Inserm U930, France.
FAU - Pierard, Christophe
AU  - Pierard C
AD  - IRBA, France.
FAU - David, Vincent
AU  - David V
AD  - Universite de Bordeaux, INCIA CNRS UMR 5287, France.
FAU - Henkous, Nadia
AU  - Henkous N
AD  - Universite de Bordeaux, INCIA CNRS UMR 5287, France.
FAU - Decorte, Laurence
AU  - Decorte L
AD  - Universite de Bordeaux, INCIA CNRS UMR 5287, France.
FAU - Mons, Nicole
AU  - Mons N
AD  - Universite de Bordeaux, INCIA CNRS UMR 5287, France.
FAU - Beracochea, Daniel
AU  - Beracochea D
AD  - Universite de Bordeaux, INCIA CNRS UMR 5287, France.
LA  - eng
PT  - Journal Article
DEP - 20160210
PL  - United States
TA  - Addict Biol
JT  - Addiction biology
JID - 9604935
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Alcoholism/blood/*complications
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Corticosterone/*blood
MH  - Disease Models, Animal
MH  - Hippocampus
MH  - Male
MH  - Memory Disorders/blood/*chemically induced
MH  - Memory, Short-Term/*drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Prefrontal Cortex/drug effects/*metabolism
MH  - Spatial Memory/*drug effects
MH  - Substance Withdrawal Syndrome/blood/*complications
OTO - NOTNLM
OT  - Alcohol withdrawal
OT  - corticosterone
OT  - hippocampus
OT  - prefrontal cortex
OT  - working memory
EDAT- 2016/02/11 06:00
MHDA- 2018/04/25 06:00
CRDT- 2016/02/11 06:00
PHST- 2015/06/17 00:00 [received]
PHST- 2015/12/16 00:00 [revised]
PHST- 2016/01/11 00:00 [accepted]
PHST- 2016/02/11 06:00 [pubmed]
PHST- 2018/04/25 06:00 [medline]
PHST- 2016/02/11 06:00 [entrez]
AID - 10.1111/adb.12371 [doi]
PST - ppublish
SO  - Addict Biol. 2017 Jul;22(4):898-910. doi: 10.1111/adb.12371. Epub 2016 Feb 10.