A suite of engineered mice for interrogating psychedelic drug actions

Area of Science:

• Neuroscience
• Pharmacology
• Genetics

Background:

• Psychedelic drugs like LSD and psilocybin show therapeutic potential for neuropsychiatric conditions.
• Classical psychedelics function by activating serotonin 2A receptors (HTR2As).
• Understanding HTR2A's role is crucial for developing psychedelic therapies.

Purpose of the Study:

• To create and validate novel mouse models for studying HTR2A's function in psychedelic drug action.
• To facilitate research into the mechanisms of psychedelic therapeutics.

Main Methods:

• Generation of Htr2a^EGFP-CreERT2 mice for visualizing HTR2A distribution.
• Development of humanized Htr2a^{A242S-EGFP-Cre} and constitutive Htr2a^Cre mice.
• Behavioral and electrophysiological assessments of psychedelic drug effects in engineered mice.

Main Results:

• Engineered mouse lines demonstrated utility in studying psychedelic effects.
• Electrophysiology confirmed psychedelic-induced neuronal firing changes in genetically identified neurons.
• HTR2A distribution in the brain was visualized using the generated mouse models.

Conclusions:

• The developed mouse lines are valuable tools for in vivo research on psychedelic mechanisms.
• These models will advance understanding of molecular, cellular, and physiological effects of psychedelics.
• This research supports the development of novel psychedelic-based treatments.