Sex-dependent developmental changes in behavior, brain structure, functional connectivity, and sensory perception...

Area of Science:

• Neuroscience
• Developmental Biology
• Psychopharmacology

Background:

• Psilocybin, a hallucinogen, induces neurobiological and behavioral changes.
• Adolescence is a critical period of heightened brain neuroplasticity, especially in the forebrain.
• Early life exposures can have lasting impacts on brain development and function.

Purpose of the Study:

• To investigate the long-term effects of adolescent psilocybin exposure on emotional behavior, neuroanatomy, neurocircuitry, and epigenetics in mice.
• To determine if psilocybin exposure during a sensitive developmental window impacts brain structure and function into adulthood.

Main Methods:

• Adolescent male and female mice received psilocybin or vehicle via oral gavage.
• Post-adolescence, mice underwent MRI (voxel-based morphometry, diffusion weighted imaging, resting-state fMRI) and behavioral tests.
• Prefrontal cortex tissue was analyzed for epigenetic and neuroplasticity protein markers.

Main Results:

• Psilocybin-exposed females showed reduced open field mobility; both sexes exhibited reduced sensitivity to rewarding/aversive stimuli.
• Regional brain volume reductions and altered water diffusivity were more pronounced in males.
• Increased global and regional functional connectivity, particularly involving the prefrontal cortex, was observed in both sexes.
• Males displayed reduced prefrontal cortex levels of epigenetic and neuroplasticity protein markers.

Conclusions:

• Adolescent psilocybin exposure leads to significant, long-term neurodevelopmental consequences.
• Observed changes include altered brain structure, enhanced functional connectivity, and modified perception of stimuli.
• Males appear more vulnerable to these long-term effects, evidenced by greater structural changes and reduced protein markers in the prefrontal cortex.