Prefrontal Electrophysiological Biomarkers and Mechanism-Based Drug Effects in a Rat Model of Alcohol Addiction
Research Square February 22, 2024 Bettina Habelt, Dzmitry Afanasenkau, Cindy Schwarz et al.
Current treatments for alcohol use disorder (AUD) are often ineffective due to large variability in individual responses and high relapse rates. A precision medicine approach using biomarkers of prefrontal control mechanisms—which are severely disrupted in AUD, reducing inhibitory control and promoting compulsive behavior and relapse—may improve outcomes. In a rat model of alcohol addiction and relapse, a biocompatible neuroprosthesis measured prefrontal neural function during abstinence. Alcohol-dependent rats showed reduced amplitudes of P1N1 and N1P2 event-related potential components and attenuated event-related oscillatory activity. Treatment with psilocybin (a 5-HT2AR agonist) or LY379268 (an mGluR2 agonist) restored these impairments. Psilocybin also counteracted a dominance in higher beta frequencies indicative of hyperarousal prone to relapse. These findings identify prefrontal markers of relapse and treatment response, particularly for psychedelic drugs.