Early handling improves sociability and preference for social novelty in social-defeated male rats: Laterality in vermal Purkinje cells architecture

Abstract

Although the cerebellum is primarily known for motor functions, its involvement in cognitive and emotional functions has become more evident in recent years. In particular, the cerebellar vermis has been implicated in social behavior. Here, we examined the effects of social defeat stress (SDS) during late adolescence on sociability, preference for social novelty, and the morphological characteristics of cerebellar Purkinje cells (PCs). Additionally, we investigated the impact of early handling, an early-life mild stress, and its interaction with subsequent SDS, on social behavior and the structure of vermal PCs. We found that socially defeated rats exhibit reduced social preference and social novelty-seeking behaviors, while early-handled rats show improved social behavior and increased resilience against SDS-induced impairments of social behavior. Structural analysis of Golgi-Cox stained vermal PCs revealed a significant reduction in dendritic spine density in socially defeated rats, especially of the stubby type. Early handling alone did not alter spine density but protected against SDS-induced spine loss. Moreover, PCs in early-handled rats exhibited a more complex dendritic arbor compared to controls. Both early-handled and socially defeated rats showed greater total dendritic cable length and a larger area under the Sholl curve for PCs in the right vermis compared to those in the left. This is the first report of lateralized effects of early life mild stress and/or later severe stress on the dendritic architecture of PCs, and a further support for the potential role of the vermis in social behavior.

Keywords: Dendrite morphology; Early handling; Laterality; Purkinje cell; Social behavior; Social defeat stress.