1. Psilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism
- Author
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Cathrin Rohleder, Georg Köhr, Anita C. Hansson, Nils Meier, Heike Endepols, Marcus W. Meinhardt, Manuela L. Meinhardt, Dusan Bartsch, Konstantin Wagner, Oliver von Bohlen und Halbach, Janet Barroso-Flores, Richard L. Bell, Mickaël Naassila, Wolfgang H. Sommer, Elisabeth Paul, Jérôme Jeanblanc, Kai Schönig, Grégory Fouquet, Simone Pfarr, Bernd Neumaier, Rebecca Hoffmann, and Rainer Spanagel
- Subjects
Multidisciplinary ,business.industry ,food and beverages ,SciAdv r-articles ,Craving ,Diseases and Disorders ,Executive functions ,Psilocybin ,medicine ,Molecular mechanism ,ddc:500 ,medicine.symptom ,Cognitive impairment ,business ,Executive dysfunction ,Clinical psychology ,medicine.drug ,Research Article ,Neuroscience - Abstract
Description, Alcohol-induced mGluR2 deficits are restored by psilocybin, resulting in a rescue of pathological behaviors in alcoholism., 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.
- Published
- 2021