Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction
Language English Country United States Media electronic
Document type Journal Article
Grant support
521379614
Deutsche Forschungsgemeinschaft (German Research Foundation)
402170461
Deutsche Forschungsgemeinschaft (German Research Foundation)
ME 5279/3-1
Deutsche Forschungsgemeinschaft (German Research Foundation)
402170461
Deutsche Forschungsgemeinschaft (German Research Foundation)
91690
Volkswagen Foundation (VolkswagenStiftung)
804005
EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
01EW1908
Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
01ZX1909A
Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
01EW1908
Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
PubMed
39639028
PubMed Central
PMC11621398
DOI
10.1038/s41398-024-03189-z
PII: 10.1038/s41398-024-03189-z
Knihovny.cz E-resources
- MeSH
- Alcoholism * drug therapy physiopathology MeSH
- Amino Acids MeSH
- Bridged Bicyclo Compounds, Heterocyclic * pharmacology MeSH
- Biomarkers MeSH
- Evoked Potentials drug effects MeSH
- Rats MeSH
- Disease Models, Animal * MeSH
- Prefrontal Cortex * drug effects physiopathology metabolism MeSH
- Psilocybin * pharmacology MeSH
- Receptors, Metabotropic Glutamate MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Amino Acids MeSH
- Bridged Bicyclo Compounds, Heterocyclic * MeSH
- Biomarkers MeSH
- LY 379268 MeSH Browser
- metabotropic glutamate receptor 2 MeSH Browser
- Psilocybin * MeSH
- Receptors, Metabotropic Glutamate MeSH
Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD. This results in reduced inhibitory control of compulsive behavior and, eventually, relapse. We reasoned here that prefrontal dysfunction, which underlies vulnerability to relapse, is evidenced by altered neuroelectric signatures and should be restored by pharmacological interventions that specifically target prefrontal dysfunction. To test this, we applied our recently developed biocompatible neuroprosthesis to measure prefrontal neural function in a well-established rat model of alcohol addiction and relapse. We monitored neural oscillations and event-related potentials in awake alcohol-dependent rats during abstinence and following treatment with psilocybin or LY379268, agonists of the serotonin 2A receptor (5-HT2AR), and the metabotropic glutamate receptor 2 (mGluR2), that are known to reduce prefrontal dysfunction and relapse. Electrophysiological impairments in alcohol-dependent rats are reduced amplitudes of P1N1 and N1P2 components and attenuated event-related oscillatory activity. Psilocybin and LY379268 were able to restore these impairments. Furthermore, alcohol-dependent animals displayed a dominance in higher beta frequencies indicative of a state of hyperarousal that is prone to relapse, which particularly psilocybin was able to counteract. In summary, we provide prefrontal markers indicative of relapse and treatment response, especially for psychedelic drugs.
Biotechnology Center Technische Universität Dresden Dresden Germany
German Center for Mental Health partner site Mannheim Heidelberg Ulm Mannheim Germany
Leibniz Institute of Polymer Research Dresden Dresden Germany
Psychedelic Research Center National Institute of Mental Health Klecany Czech Republic
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