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Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction

. 2024 Dec 05 ; 14 (1) : 486. [epub] 20241205

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)

Links

PubMed 39639028
PubMed Central PMC11621398
DOI 10.1038/s41398-024-03189-z
PII: 10.1038/s41398-024-03189-z
Knihovny.cz E-resources

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.

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