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000904392 1001_ $$00000-0002-5103-0731$$aMeinhardt, Marcus W.$$b0$$eCorresponding author
000904392 245__ $$aPsilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism
000904392 260__ $$aWashington, DC [u.a.]$$bAssoc.$$c2021
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000904392 520__ $$aAlcohol-dependent patients commonly show impairments in executive functions that facilitate craving and can lead to relapse. However, the molecular mechanisms leading to executive dysfunction in alcoholism are poorly understood, and new effective pharmacological treatments are desired. Here, using a bidirectional neuromodulation approach, we demonstrate a causal link between reduced prefrontal mGluR2 function and both impaired executive control and alcohol craving. A neuron-specific prefrontal mGluR2 knockdown in rats generated a phenotype of reduced cognitive flexibility and excessive alcohol seeking. Conversely, virally restoring prefrontal mGluR2 levels in alcohol-dependent rats rescued these pathological behaviors. In the search for a pharmacological intervention with high translational potential, psilocybin was capable of restoring mGluR2 expression and reducing relapse behavior. Last, we propose a FDG-PET biomarker strategy to identify mGluR2 treatment-responsive individuals. In conclusion, we identified a common molecular pathological mechanism for both executive dysfunction and alcohol craving and provided a personalized mGluR2 mechanism-based intervention strategy for medication development for alcoholism.
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000904392 7001_ $$0P:(DE-HGF)0$$aPfarr, Simone$$b1
000904392 7001_ $$00000-0003-0790-1197$$aFouquet, Grégory$$b2
000904392 7001_ $$00000-0002-3559-1846$$aRohleder, Cathrin$$b3
000904392 7001_ $$0P:(DE-HGF)0$$aMeinhardt, Manuela L.$$b4
000904392 7001_ $$00000-0002-2804-6188$$aBarroso-Flores, Janet$$b5
000904392 7001_ $$0P:(DE-HGF)0$$aHoffmann, Rebecca$$b6
000904392 7001_ $$00000-0003-0353-2777$$aJeanblanc, Jérôme$$b7
000904392 7001_ $$00000-0002-0201-273X$$aPaul, Elisabeth$$b8
000904392 7001_ $$00000-0002-9894-1030$$aWagner, Konstantin$$b9
000904392 7001_ $$0P:(DE-HGF)0$$aHansson, Anita C.$$b10
000904392 7001_ $$00000-0001-6768-3545$$aKöhr, Georg$$b11
000904392 7001_ $$0P:(DE-HGF)0$$aMeier, Nils$$b12
000904392 7001_ $$00000-0002-2613-2517$$avon Bohlen und Halbach, Oliver$$b13
000904392 7001_ $$00000-0002-0525-0485$$aBell, Richard L.$$b14
000904392 7001_ $$0P:(DE-Juel1)180330$$aEndepols, Heike$$b15$$ufzj
000904392 7001_ $$0P:(DE-Juel1)166419$$aNeumaier, Bernd$$b16
000904392 7001_ $$00000-0003-3754-408X$$aSchönig, Kai$$b17
000904392 7001_ $$00000-0002-1140-9923$$aBartsch, Dusan$$b18
000904392 7001_ $$00000-0002-9788-0918$$aNaassila, Mickaël$$b19
000904392 7001_ $$00000-0003-2151-4521$$aSpanagel, Rainer$$b20$$eCorresponding author
000904392 7001_ $$00000-0002-5903-6521$$aSommer, Wolfgang H.$$b21$$eCorresponding author
000904392 773__ $$0PERI:(DE-600)2810933-8$$a10.1126/sciadv.abh2399$$gVol. 7, no. 47, p. eabh2399$$n47$$peabh2399$$tScience advances$$v7$$x2375-2548$$y2021
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