Universität zu Köln

Meinhardt, Marcus W., Pfarr, Simone, Fouquet, Gregory, Rohleder, Cathrin, Meinhardt, Manuela L., Barroso-Flores, Janet ORCID: 0000-0002-2804-6188, Hoffmann, Rebecca, Jeanblanc, Jerome ORCID: 0000-0003-0353-2777, Paul, Elisabeth ORCID: 0000-0002-0201-273X, Wagner, Konstantin ORCID: 0000-0002-9894-1030, Hansson, Anita C., Koehr, Georg, Meier, Nils, Halbach, Oliver von Bohlen und, Bell, Richard L., Endepols, Heike, Neumaier, Bernd, Schoenig, Kai, Bartsch, Dusan, Naassila, Mickael, Spanagel, Rainer and Sommer, Wolfgang H. (2021). Psilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism. Sci. Adv., 7 (47). WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 2375-2548

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Meinhardt, Marcus W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfarr, Simone UNSPECIFIED UNSPECIFIED UNSPECIFIED Fouquet, Gregory UNSPECIFIED UNSPECIFIED UNSPECIFIED Rohleder, Cathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Meinhardt, Manuela L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Barroso-Flores, Janet UNSPECIFIED orcid.org/0000-0002-2804-6188 UNSPECIFIED Hoffmann, Rebecca UNSPECIFIED UNSPECIFIED UNSPECIFIED Jeanblanc, Jerome UNSPECIFIED orcid.org/0000-0003-0353-2777 UNSPECIFIED Paul, Elisabeth UNSPECIFIED orcid.org/0000-0002-0201-273X UNSPECIFIED Wagner, Konstantin UNSPECIFIED orcid.org/0000-0002-9894-1030 UNSPECIFIED Hansson, Anita C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koehr, Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Meier, Nils UNSPECIFIED UNSPECIFIED UNSPECIFIED Halbach, Oliver von Bohlen und UNSPECIFIED UNSPECIFIED UNSPECIFIED Bell, Richard L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Endepols, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED Neumaier, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Schoenig, Kai UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartsch, Dusan UNSPECIFIED UNSPECIFIED UNSPECIFIED Naassila, Mickael UNSPECIFIED UNSPECIFIED UNSPECIFIED Spanagel, Rainer UNSPECIFIED UNSPECIFIED UNSPECIFIED Sommer, Wolfgang H. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-600020
DOI:	10.1126/sciadv.abh2399
Journal or Publication Title:	Sci. Adv.
Volume:	7
Number:	47
Date:	2021
Publisher:	AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication:	WASHINGTON
ISSN:	2375-2548
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language METABOTROPIC GLUTAMATE RECEPTORS; POSITIVE ALLOSTERIC MODULATOR; HALLUCINOGENIC DRUG; AGONIST LY379268; ANIMAL-MODELS; RATS; REINSTATEMENT; FLEXIBILITY; SENSITIVITY; PHYSIOLOGY Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60002