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@ARTICLE{Meinhardt:904392,
author = {Meinhardt, Marcus W. and Pfarr, Simone and Fouquet,
Grégory and Rohleder, Cathrin and Meinhardt, Manuela L. and
Barroso-Flores, Janet and Hoffmann, Rebecca and Jeanblanc,
Jérôme and Paul, Elisabeth and Wagner, Konstantin and
Hansson, Anita C. and Köhr, Georg and Meier, Nils and von
Bohlen und Halbach, Oliver and Bell, Richard L. and
Endepols, Heike and Neumaier, Bernd and Schönig, Kai and
Bartsch, Dusan and Naassila, Mickaël and Spanagel, Rainer
and Sommer, Wolfgang H.},
title = {{P}silocybin targets a common molecular mechanism for
cognitive impairment and increased craving in alcoholism},
journal = {Science advances},
volume = {7},
number = {47},
issn = {2375-2548},
address = {Washington, DC [u.a.]},
publisher = {Assoc.},
reportid = {FZJ-2021-05962},
pages = {eabh2399},
year = {2021},
abstract = {Alcohol-dependent patients commonly show impairments in
executive functions that facilitate craving and can lead to
relapse. However, the molecular mechanisms leading to
executive dysfunction in alcoholism are poorly understood,
and new effective pharmacological treatments are desired.
Here, using a bidirectional neuromodulation approach, we
demonstrate a causal link between reduced prefrontal mGluR2
function and both impaired executive control and alcohol
craving. A neuron-specific prefrontal mGluR2 knockdown in
rats generated a phenotype of reduced cognitive flexibility
and excessive alcohol seeking. Conversely, virally restoring
prefrontal mGluR2 levels in alcohol-dependent rats rescued
these pathological behaviors. In the search for a
pharmacological intervention with high translational
potential, psilocybin was capable of restoring mGluR2
expression and reducing relapse behavior. Last, we propose a
FDG-PET biomarker strategy to identify mGluR2
treatment-responsive individuals. In conclusion, we
identified a common molecular pathological mechanism for
both executive dysfunction and alcohol craving and provided
a personalized mGluR2 mechanism-based intervention strategy
for medication development for alcoholism.},
cin = {INM-5},
ddc = {500},
cid = {I:(DE-Juel1)INM-5-20090406},
pnm = {5253 - Neuroimaging (POF4-525)},
pid = {G:(DE-HGF)POF4-5253},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34788104},
UT = {WOS:000720347400007},
doi = {10.1126/sciadv.abh2399},
url = {https://juser.fz-juelich.de/record/904392},
}