Classification of psychedelic drugs based on brain-wide imaging of cellular c-Fos expression.
Farid AboharbPasha A DavoudianLing-Xiao ShaoClara LiaoGillian N RzepkaCassandra WojtasiewiczMark DibbsJocelyne RondeauAlexander M SherwoodAlfred P KayeAlex C KwanPublished in: bioRxiv : the preprint server for biology (2024)
Psilocybin, ketamine, and MDMA are psychoactive compounds that exert behavioral effects with distinguishable but also overlapping features. The growing interest in using these compounds as therapeutics necessitates preclinical assays that can accurately screen psychedelics and related analogs. We posit that a promising approach may be to measure drug action on markers of neural plasticity in native brain tissues. We therefore developed a pipeline for drug classification using light sheet fluorescence microscopy of immediate early gene expression at cellular resolution followed by machine learning. We tested male and female mice with a panel of drugs, including psilocybin, ketamine, 5-MeO-DMT, 6-fluoro-DET, MDMA, acute fluoxetine, chronic fluoxetine, and vehicle. In one-versus-rest classification, the exact drug was identified with 66% accuracy, significantly above the chance level of 12.5%. In one-versus-one classifications, psilocybin was discriminated from 5-MeO-DMT, ketamine, MDMA, or acute fluoxetine with >95% accuracy. We used Shapley additive explanation to pinpoint the brain regions driving the machine learning predictions. Our results support a novel approach for screening psychoactive drugs with psychedelic properties.
Keyphrases
- machine learning
- drug induced
- gene expression
- deep learning
- artificial intelligence
- white matter
- resting state
- liver failure
- single molecule
- high throughput
- big data
- high resolution
- pain management
- adverse drug
- poor prognosis
- dna methylation
- emergency department
- mesenchymal stem cells
- adipose tissue
- aortic dissection
- hepatitis b virus
- positron emission tomography
- computed tomography
- intensive care unit
- density functional theory
- molecular docking
- optical coherence tomography
- acute respiratory distress syndrome
- pet ct