Prefrontal Electrophysiological Biomarkers and Mechanism-Based Drug Effects in a Rat Model of Alcohol Addiction
Bettina Habelt, Dzmitry Afanasenkau, Cindy Schwarz, Kevin Domanegg, Martin Kuchař, Carsten Werner, Ivan R. Minev, Rainer Spanagel, Marcus W. Meinhardt, Nadine Bernhardt
Research Square February 22, 2024 preprint DOI: 10.21203/rs.3.rs-3905152/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study in an animal model |
|---|---|
| Population | Awake alcohol-dependent rats in a model of alcohol addiction and relapse |
| Interventions | Psilocybin LY379268 |
| Topics | Addiction |
| Keywords | Prefrontal cortex Electrophysiology Alcohol dependence |
| Key findings | Psilocybin and LY379268 restore electrophysiological impairments in prefrontal neural function in alcohol-dependent rats, and psilocybin counteracts hyperarousal indicated by higher beta frequency dominance. |
Abstract
Abstract Current treatments for alcohol use disorder (AUD) show large heterogeneity in response and thus limited effectiveness and high relapse rates. 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.
Comparable studies
Other preclinical and animal studies on addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Rats | 2005 | Experimental study | |
| Effects of ibogaine on acute signs of morphine withdrawal in rats: independence from tremor. Morphine-dependent rats | 1992 | Randomized controlled trial | |
| Structure-based discovery of conformationally selective inhibitors of the serotonin transporter. Mice | 2023 | Computational docking and experimental validation | |
| Reinforcing Effects of MDMA (‘Ecstasy’) in Drug-Naive and Cocaine-Trained Rats Rats | 2001 | Experimental study |
Citations in the library
Cites 6
- Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder JAMA Psychiatry August 24, 2022
- Psilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism Science Advances November 17, 2021
- Psilocybin and LSD have no long-lasting effects in an animal model of alcohol relapse Neuropsychopharmacology May 5, 2020
- Psilocin, LSD, mescaline, and DOB all induce broadband desynchronization of EEG and disconnection in rats with robust translational validity Translational Psychiatry October 2, 2021
- Psychedelic Targeting of Metabotropic Glutamate Receptor 2 and Its Implications for the Treatment of Alcoholism Cells March 22, 2023
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