TY  - JOUR
AU  - Meinhardt, Marcus W.
AU  - Pfarr, Simone
AU  - Fouquet, Grégory
AU  - Rohleder, Cathrin
AU  - Meinhardt, Manuela L.
AU  - Barroso-Flores, Janet
AU  - Hoffmann, Rebecca
AU  - Jeanblanc, Jérôme
AU  - Paul, Elisabeth
AU  - Wagner, Konstantin
AU  - Hansson, Anita C.
AU  - Köhr, Georg
AU  - Meier, Nils
AU  - von Bohlen und Halbach, Oliver
AU  - Bell, Richard L.
AU  - Endepols, Heike
AU  - Neumaier, Bernd
AU  - Schönig, Kai
AU  - Bartsch, Dusan
AU  - Naassila, Mickaël
AU  - Spanagel, Rainer
AU  - Sommer, Wolfgang H.
TI  - Psilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism
JO  - Science advances
VL  - 7
IS  - 47
SN  - 2375-2548
CY  - Washington, DC [u.a.]
PB  - Assoc.
M1  - FZJ-2021-05962
SP  - eabh2399
PY  - 2021
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:34788104
UR  - <Go to ISI:>//WOS:000720347400007
DO  - DOI:10.1126/sciadv.abh2399
UR  - https://juser.fz-juelich.de/record/904392
ER  -