Stress alters social functioning in a complex manner. An important variable determining the final effects of stress is stressor intensity. However, the precise relationship between stressor intensity and social behavior is not well understood. Here we investigate the effects of varying acute stressor intensity exposure on social behavior using adult zebrafish. We first establish a novel test using adult zebrafish that allows distinguishing fish's drive to approach a social cue and its ability to engage and maintain social interaction within the same behavioral paradigm. Next, we combined this test with a new method to deliver an acute stress stimulus or varying intensities. Our results show that both social approach and social maintenance are reduced in adult zebrafish upon acute stress exposure in an intensity-dependent manner. Interestingly, lower stress intensity reduces social maintenance without affecting the social approach, while a higher stress level is required to alter social approach. These results provide evidence for a direct correlation between acute stressor intensity and social functioning and suggest that distinct steps in social behavior are modulate differentially by the acute stress level.

Chronic or severe stress exposure during development primes an individual for altered stress sensitivity in adulthood and increases psychiatric disease susceptibility. However, the identity and function of genes affected by developmental stress exposure are poorly understood. Here, we used an optogenetic zebrafish model to identify brain-wide molecular alterations caused by chronic Glucocorticoid (GC) exposure during development and following subsequent exposure to an acute stressor in adulthood. We show that developmental GC-exposed fish display wide-ranging behavioral changes affecting social behavior, food consumption, and associative learning. The brain transcriptome of GC-exposed fish showed alteration of genes associated with DNA metabolism, axon development, and social behavior-related genes such as oxytocin across the life course. Strikingly, when GC-exposed fish were subjected to a stress challenge in adulthood, they showed exaggerated endocrine responses and a great number of brain-wide transcriptional changes, including gene sets associated with axon development, neuronal signaling, and epigenetic modulators. These altered gene sets showed an overrepresentation of genes linked to human psychiatric disorders. In short, our study provides a unique resource of long-term, time-dependent gene expression changes induced by developmental GC-exposure and identifies novel GC-primed genes which may shape adult responses of early life stress-exposed individuals.