Structural remodeling of medium spiny neurons in the tail of the striatum and stress-related behavioral alterations after early handling and adolescent stress in male rats.

The tail of the striatum (TS), the most distal part of the striatum, integrates sensory and value-based information and plays a critical role in threat responses. However, its vulnerability to stress remains underexplored. Here, we examined the effects of early handling (EH), chronic social defeat stress (SD) in late adolescence, and their combination (EH-SD) on anxiety- and depression-like behaviors, as well as dendritic morphology and spine density of TS medium spiny neurons (MSNs) in male rats. SD induced anxiety- and depression-like behaviors in the elevated plus maze and forced swim test, whereas EH conferred resilience against these effects. Structural analysis of Golgi-Cox-stained MSNs revealed that EH and EH-SD increased average dendritic process length without affecting branching or total dendritic length. SD markedly elevated dendritic spine density, while EH reduced it; combined EH-SD prevented the SD-induced increase. Although the changes in the total length of dendritic spines in MSNs did not reach a significant level between groups, there was a trend towards increase in the EH and EH-SD groups and a decrease in the SD group, leading to an estimate of the total number of MSN spines did not differ between groups. It seems that EH promotes structural adaptations linked to circuit stabilization, whereas SD enhances excitatory connectivity of TS MSNs, potentially heightening sensitivity to stress-related sensory inputs. Together, the findings identify the TS as a critical site of structural plasticity in stress and early-life experience, and suggest a link between MSN morphology and resilience or vulnerability to stress-related behavioral outcomes.