Developmental changes in brain structure and function following exposure to oral LSD during adolescence

Area of Science:

• Neuroscience
• Neurobiology
• Developmental Psychology

Background:

• Lysergic acid diethylamide (LSD) is a potent hallucinogen known to induce complex neurobiological and behavioral effects.
• These effects are thought to be mediated by alterations in brain neuroplasticity.
• Periadolescence represents a critical window of heightened neuroplasticity, particularly in the forebrain.

Purpose of the Study:

• To investigate the long-term developmental effects of LSD exposure during periadolescence on brain structure and function.
• To examine the impact of single and multiple LSD doses on cognitive and emotional behavior, neuroanatomy, and neurocircuitry.
• To determine if LSD exposure during this sensitive developmental period leads to lasting changes in the brain.

Main Methods:

• Female and male mice received vehicle, single, or multiple doses of LSD (3.3 µg) via oral gavage starting on postnatal day 51.
• Between postnatal days 90-120, mice underwent MRI (voxel-based morphometry, diffusion-weighted imaging, resting-state fMRI) and behavioral testing for cognition and motor function.
• MRI data were analyzed using a 3D mouse brain atlas to identify site-specific differences in brain structure and functional connectivity.

Main Results:

• Periadolescent LSD exposure did not significantly affect motor behavior or cognitive performance in young adult mice.
• Brain volume differences between experimental groups were minimal and not localized to specific regions.
• Multiple LSD exposures significantly altered gray matter microarchitecture, particularly in the thalamus, sensory/motor cortices, and basal ganglia, as indicated by diffusion-weighted imaging (DWI) changes.
• Functional connectivity was reduced between forebrain white matter tracts and sensorimotor cortices/hippocampus following multidose LSD exposure.

Conclusions:

• While LSD exposure in periadolescent mice did not yield observable deficits in cognitive or motor behavior, it induced significant alterations in brain microarchitecture and functional connectivity.
• The observed changes in gray matter microarchitecture and reduced functional connectivity suggest lasting impacts on neuroplasticity and neural circuitry.
• Further research is needed to fully elucidate the behavioral consequences of these LSD-induced neurobiological changes.