The effects of exogenous melatonin and melatonin receptor blockade on aggression and estrogen-dependent gene expression in male California mice (Peromyscus californicus).

Photoperiodic regulation of aggression has been well established in several vertebrate species, with rodents demonstrating increased aggression in short day photoperiods as compared to long day photoperiods. Previous work suggests that estrogens regulate aggression via rapid nongenomic pathways in short days and act more slowly in long days, most likely via genomic pathways. The current study therefore examines the role of melatonin in mediating aggression and estrogen-dependent gene transcription. In Experiment 1, male California mice were housed under long day photoperiods and were treated with either 0.3 µg/g of melatonin, 40 mg/kg of the melatonin receptor antagonist luzindole, or vehicle for 10 days. We found that melatonin administration significantly increased aggression as compared to mice receiving vehicle, but this phenotype was not completely ameliorated by luzindole. In Experiment 2, male California mice were injected with either 1mg/kg of the aromatase inhibitor letrozole or vehicle, and oxytocin receptor (OTR), estrogen receptor alpha (ERα), and c-fos gene expression was examined in the bed nucleus of the stria terminalis (BNST) and medial preoptic area (MPOA). In the BNST, but not MPOA, OTR mRNA was significantly downregulated following letrozole administration, indicating that OTR is an estrogen-dependent gene in the BNST. In contrast, ERα was not estrogen dependent in either brain region. In the MPOA, OTR mRNA was inhibited by melatonin, and luzindole suppressed this effect. C-fos and ERα did not differ between treatments in any brain region examined. These results suggest that it is unlikely that melatonin facilitates aggression via broad spectrum regulation of estrogen-dependent gene expression. Instead, melatonin may act via regulation of other transcription factors such as extracellular signal regulated kinase.

Paternal aggression in a biparental mouse: parallels with maternal aggression.

Environmental and social factors have important effects on aggressive behaviors. We examined the effect of reproductive experience on aggression in a biparental species of mouse, Peromyscus californicus. Estrogens are important in mediating aggressive behavior so we also examined estrogen receptor expression and c-fos for insights into possible mechanisms of regulation. Parental males were significantly more aggressive than virgin males, but no significant differences in estrogen receptor alpha or beta expression were detected. Patterns of c-fos following aggression tests suggested possible parallels with maternal aggression. Parental males had more c-fos positive cells in the medial amygdala, and medial preoptic area relative to virgin males. The medial preoptic area is generally considered to be relatively less important for male-male aggression in rodents, but is known to have increased activity in the context of maternal aggression. We also demonstrated through habituation-dishabituation tests that parental males show exaggerated investigation responses to chemical cues from a male intruder, suggesting that heightened sensory responses may contribute to increased parental aggression. These data suggest that, in biparental species, reproductive experience leads to the onset of paternal aggression that may be analogous to maternal aggression.

The progesterone challenge: steroid hormone changes following a simulated territorial intrusion in female Peromyscus californicus.

There is a growing body of evidence that the rapid but transient increase in male androgens, particularly testosterone (T), following a single social encounter such as a territorial intrusion occurs in a wide array of vertebrate taxa. Yet, this phenomenon, often called the Challenge Hypothesis, has rarely been investigated in females. Moreover, when studying male challenge effects, researchers have rarely investigated other hormones that can be important to the expression of aggression, such as progesterone (P4) and estradiol (E2). We conducted 10-min aggression trials using the resident-intruder paradigm in cycling female California mice, Peromyscus californicus, a species in which both sexes show territorial behavior. By comparing the hormone levels of test females to control females, we found a decrease in P(4) and the P4/T ratio, but no change in T, E2, corticosterone, E2/P4, or E2/T. Interestingly, these hormone changes were observed even when the resident was not aggressive toward the intruder, suggesting that the stimulus cueing the hormone changes was the mere presence of the intruder and not the amount of aggression displayed by the resident. Generally, T has a positive relationship with aggression, whereas P4 inhibits male and nonmaternal female aggression. Thus, decreasing the P4/T ratio following an encounter may serve to increase future aggression in females. These results suggest that females may use different hormonal mechanisms than do males to mediate aggression in a challenge situation.

Testosterone promotes paternal behaviour in a monogamous mammal via conversion to oestrogen.

Although high testosterone (T) levels inhibit paternal behaviour in birds breeding in temperate zones many paternal mammals have a very different breeding biology, characterized by a post-partum oestrus. In species with post-partum oestrus, males may engage in T-dependent behaviours such as aggression and copulation simultaneously with paternal behaviour. We previously found that T promotes paternal behaviour in the California mouse, Peromyscus californicus. We examine whether this effect is mediated by the conversion of T to oestradiol (E(2)) by aromatase. In the first experiment, gonadectomized males treated with T or E(2) implants showed higher levels of huddling and pup grooming behaviour than gonadectomized males treated with dihydrotestosterone or empty implants. In the second experiment, we used an aromatase inhibitor (fadrozole) (FAD) to confirm these results. Gonadectomized males treated with T + vehicle or E(2) + FAD showed higher levels of huddling and pup grooming behaviour than gonadectomized males treated with T + FAD or empty implants. Although E(2) is known to promote the onset of maternal behaviour to our knowledge our results are the first to demonstrate that E(2) can promote paternal behaviour in a paternal mammal. These results may explain how mammals express paternal behaviour while T levels are elevated.