Synaptic reorganization following developmental exposure to substances of abuse: A scoping review of preclinical models

Background: The development of the brain involves extensive structuring of neural circuit architecture. Exposure to addictive substances during this period may disrupt brain maturation, increasing vulnerability to psychopathology. Synaptic pruning (i.e. a key process refining neural circuits) is particularly sensitive to environmental factors, including substance exposure. Although substance-related changes in synapse organization are well documented in adults, effects during early development remain poorly characterized. The aim of this review is to determine whether exposure to addictive substances during key developmental stages altersalter markers of synaptic organization in animal models. Methods: A scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Preclinical studies investigating changes to dendritic spines or synaptic protein markers in animals before postnatal day 50 were included. Comprehensive searches were performed in MEDLINE®, Embase, CINAHL, PsycINFO®, and Scopus from database inception to February 2024. Results: From 8256 publications, only 34 studies met inclusion criteria. Limited findings suggest that stimulant exposure in juvenile rodents may increase dendritic spine measures in striatal regions. Our results also suggest that alcohol increases presynaptic markers and immature spines, but may decrease post-synaptic markers and mature spines. Finally, neonatal alcohol, and juvenile to adolescent stimulant and THC exposure are moderately associated with reductions in dendritic spine density in the frontal cortex. Conclusions: Substance exposure during early brain development may alter synaptic structure and proteins important for brain function. Further investigation of pre- and post-synaptic elements is required to better understand synaptic alterations in the developing brain.