Neurobiological effects of psychedelics in the mouse

Psychedelic compounds such as psilocybin and LSD induce hallucinatory effects via 5-HT_2A receptors in humans. In mice, they induce typical head-twitching behavior and induce activation of specific brain areas. This thesis project aims to better characterize in vivo effects of psychedelic compounds and to understand molecular consequences of the drug effects. The student will establish an in vivo imaging method (fiber photometry) to assess pharmacokinetics of psychedelics as well as their acute effects on neuromodulators and neuronal activity. Further, in situ hybridization and immunofluorescence will be used to investigate molecular effects in brain tissue from mice treated with psychedelics. The project also involves video analysis of mouse behavior and hands on with animal experiments (mice) after the required training.

Acute effects of psychedelics in mice

Psychedelic compounds such as psilocybin and LSD induce hallucinatory effects in humans. In mice, a characteristic behavior arising from acute treatment with psychedelics is increased head twitching, which is commonly used as pre-clinical read-out for hallucinatory efficacy in drug development for psychedelics analogs. The goal of this Master thesis is the analysis of videos from mice under the influence of psilocybin and other psychedelics using manual experimenter scoring and advanced image analysis tools. In parallel, with immunofluorescence staining of mouse tissue, changes of protein expression arising from psychedelic exposure will be assessed and brain areas and cell types identified, working towards a refined picture of acute drug effects in the brain.

Antidepressant effects of psychedelics investigated in the mouse model

Psychedelics have the potential for the clinical application in mental disorders. Clinical trials are ongoing to investigate the therapeutic potential of psilocybin, but the mode of action is not well understood. It has been hypothesized that neuronal plasticity is involved in these effects, yet more research is needed to understand the cellular identity of involved neuronal networks. In this project, preclinical antidepressant testing will be analyzed, which involves computational video analysis of previously conducted tests with mice treated with psychedelics. Furthermore, the tissue from treated mice will be assessed in the laboratory (e.g. immunostaining, in situ hybridization) identifying long-term molecular effects in the mouse brain from the treatment with psychedelics.