Data for: Melatonin-dependent changes in neurosteroids are associated with increased aggression in a seasonally breeding rodent

Aggression is a complex social behavior that allows individuals to compete for access to limited resources (e.g., mates, food, and territories). Excessive or inappropriate aggression, however, has become problematic in modern societies, and current treatments are largely ineffective. While previous work in mammals suggests that aggressive behavior varies seasonally, seasonality is largely overlooked when developing clinical treatments for inappropriate aggression. Here, we investigated how the hormone melatonin regulates seasonal changes in neurosteroid levels and aggressive behavior in Siberian hamsters, a rodent model of seasonal aggression. Specifically, we housed males in long-day (LD) or short-day (SD) photoperiods, administered timed subcutaneous melatonin injections (which mimic a SD-like signal) or control injections, and measured aggression using a resident-intruder paradigm after 9 weeks of treatment. Moreover, we quantified five steroid hormones in circulation and in brain regions associated with aggressive behavior (lateral septum, anterior hypothalamus, medial amygdala, and periaqueductal gray) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). SD hamsters and LD hamsters administered timed melatonin injections (LD-M) displayed increased aggression and exhibited region-specific decreases in neural dehydroepiandrosterone, testosterone, and estradiol, but showed no changes in progesterone or cortisol. Male hamsters also showed distinct associations between neurosteroids and aggressive behavior, in which neural progesterone and dehydroepiandrosterone were positively correlated with aggression in all treatment groups, whereas neural testosterone, estradiol, and cortisol were negatively correlated with aggression only in LD-M and SD hamsters. Collectively, these results provide insight into a novel neuroendocrine mechanism of mammalian aggression, in which melatonin reduces neurosteroid levels and increases aggressive behavior.