Melatonin‐dependent changes in neurosteroids are associated with increased aggression in a seasonally breeding rodent

Abstract

Aggression is a complex social behaviour that allows individuals to compete for access to limited resources (eg, mates, food and territories). Excessive or inappropriate aggression, however, has become problematic in modern societies, and current treatments are largely ineffective. Although previous work in mammals suggests that aggressive behaviour 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 behaviour in Siberian hamsters, a rodent model of seasonal aggression. Specifically, we housed males in long-day (LD) or short-day (SD) photoperiods, administered timed s.c. 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 behaviour (lateral septum, anterior hypothalamus, medial amygdala and periaqueductal gray) using liquid chromatography-tandem mass spectrometry. SD hamsters and LD hamsters administered timed melatonin injections (LD-M) displayed increased aggression and exhibited region-specific decreases in neural dehydroepiandrosterone, testosterone and oestradiol, but showed no changes in progesterone or cortisol. Male hamsters also showed distinct associations between neurosteroids and aggressive behaviour, in which neural progesterone and dehydroepiandrosterone were positively correlated with aggression in all treatment groups, whereas neural testosterone, oestradiol 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 elevates aggressive behaviour.

The ontogeny of personality: Repeatability of social and escape behaviors across developmental stages in Siberian hamsters (Phodopus sungorus)

“…We investigated individual consistency in social and escape behaviors across ontogeny using Siberian hamsters (Phodopus sungorus), which is an ideal, non-model system in which to test individual consistency in behavioral traits across time. Social and escape behaviors have been well documented in our lab population in both juveniles (Cusick et al, in review) and adults (Cusick et al in prep;Munley et al, 2021;Scotti et al, 2008;Sylvia et al, 2017), and are comparable to behaviors in wild populations (Ross, 1998). Social (e.g., aggressiveness, investigation) and escape behaviors are commonly measured traits in animal personality (e.g., Cabrera et al, 2021).…”

Sex-specific endocrine regulation of seasonal aggression in Siberian hamsters

“…Two-way multivariate analyses of variance (MANOVAs) were used to assess the effects of melatonin and photoperiodic treatment, sex, and the interaction between treatment and sex on PROG synthesis, AE synthesis, and the ratio of AE:PROG synthesis across tissues and brain regions. If a multivariate test reported a significant effect or a trend towards a significant effect ( p < 0.10) of treatment, sex, and/or the interaction between treatment and sex for one or more of the variables included in an analysis, two-way ANOVAs or generalized linear models (GLMs) and post-hoc testing (Tukey's HSD tests for two-way ANOVAs and Dunn's tests for GLMs) were conducted to examine pairwise comparisons (electronic supplementary material) [15,27].…”

“…We have shown that LD male and female hamsters given timed melatonin injections, which mimic an SD-like melatonin signal in circulation, show higher levels of aggression than LD hamsters given control injections and exhibit SD-like variation in baseline and aggression-induced circulating androgen and oestrogen levels [13,14]. We have also demonstrated that timed melatonin administration and exposure to SDs decreases concentrations of DHEA, T and E 2 in brain regions associated with aggression in male hamsters, including the anterior hypothalamus (AH) and periaqueductal gray (PAG) [15]. Recently, we determined that lentiviral-mediated overexpression of the MT 1 melatonin receptor, the primary melatonin receptor in Siberian hamsters, in the adrenal glands causes SD-like increases in aggression in male hamsters, but does not alter circulating DHEA levels [16], which could suggest that adrenal MT 1 receptors regulate seasonal aggression directly via neural substrates.…”

“…investigation, self-grooming). Moreover, we quantified the synthesis of progesterone and androstenedione via 3β-HSD in the adrenal glands and the AH and PAG, two brain regions associated with aggression which we have previously shown to exhibit seasonal and melatonin-dependent changes in neurosteroid levels in male hamsters [15,21], using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We hypothesized that melatonin mediates increased aggression during the non-breeding season by elevating adrenal DHEA secretion and the conversion of prohormones (i.e.…”

Neuroendocrine mechanisms of aggression in rodents.

“…During the winter months when resources are more limited and temperatures are low, animals tend to dedicate more energy to survival rather than reproduction (Walton et al, 2011). Aggression is a social behavior often crucial for survival as animals compete for limited resources and defend their territory (Munley et al, 2021). Because of the relationship between steroid hormones and aggression, the alteration or maintenance of aggression from the reproductive to nonreproductive seasons is of particular interest (Duque-Wilckens et al, 2019).…”