Matthew J. Fuxjager

Testosterone release and social context: When it occurs and why

The functions of rapid increases in testosterone seem paradoxical because they can occur in response to different social contexts, such as male-male aggressive encounters and male-female sexual encounters. This suggests that context may impact the functional consequences of changes in testosterone, whether transient or long term. Many studies, including those with California mice (Peromyscus californicus), have addressed these issues using manipulations and species comparisons, but many areas remain to be investigated. We report a study here that suggests transient increases in testosterone after social competition influence future competitive behavior, but social experience alone may also be critical in determining future behavior. In other rodents, a comparable testosterone surge occurs in response to sexual stimulation, but the function is not entirely understood. In addition to competitive and sexual behavior, testosterone impacts other systems instrumental to social behaviors, including paternal behavior and degree of monogamy. Thus, mechanisms regulated by testosterone, such as the vasopressin and aromatase systems, may also be influenced by rapid surges of testosterone in aggressive or sexual contexts. We discuss how the functions of testosterone may overlap in some contexts.

Winning territorial disputes selectively enhances androgen sensitivity in neural pathways related to motivation and social aggression

Winning aggressive disputes can enhance future fighting ability and the desire to seek out additional contests. In some instances, these effects are long lasting and vary in response to the physical location of a fight. Thus, in principle, winning aggressive encounters may cause long-term and context-dependent changes to brain areas that control the output of antagonistic behavior or the motivation to fight (or both). We examined this issue in the territorial California mouse (Peromyscus californicus) because males of this species are more likely to win fights after accruing victories in their home territory but not after accruing victories in unfamiliar locations. Using immunocytochemistry and real-time quantitative PCR, we found that winning fights either at home or away increases the expression of androgen receptors (AR) in the medial anterior bed nucleus of the stria terminalis, a key brain area that controls social aggression. We also found that AR expression in brain regions that mediate motivation and reward, nucleus accumbens (NAcc) and ventral tegmental area (VTA), increases only in response to fights in the home territory. These effects of winning were likely exclusive to the neural androgenic system because they have no detectible impact on the expression of progestin receptors. Finally, we demonstrated that the observed changes in androgen sensitivity in the NAcc and VTA are positively associated with the ability to win aggressive contests. Thus, winning fights can change brain phenotype in a manner that likely promotes future victory and possibly primes neural circuits that motivate individuals to fight.

The 'home advantage' is necessary for a full winner effect and changes in post-encounter testosterone

Winning aggressive contests can both enhance future winning ability and change post-encounter hormones; however, it remains unclear if the context of a fight also influences such winner effects and hormone changes. We investigated this issue by using California mice (Peromyscus californicus) to test if the effect of residency status is necessary to improve future winning ability and alter post-encounter hormones. Male mice were subjected to an aggressive contest and their blood was collected 45 min after the fight. Upon contest initiation, focal mice had a home advantage and three prior winning experiences, only one of these factors, or neither factor. Only individuals with a home advantage and prior winning experience showed a full winner effect. Post-encounter changes in testosterone and progesterone resulted from an interaction between residency status and winning experience. These data indicate that in male California mice a home advantage is necessary to produce the full winner effect and that residency status helps regulate inter-individual variation in the expression of post-encounter testosterone pulses and progesterone changes. Furthermore, these respective behavioral and physiological phenomena might be modulated in a context-specific manner, in part by the surrounding physical environment.

Independent and Additive Contributions of Postvictory Testosterone and Social Experience to the Development of the Winner Effect

The processes through which salient social experiences influence future behavior are not well understood. Winning fights, for example, can increase the odds of future victory, yet little is known about the internal mechanisms that underlie such winner effects. Here, we use the territorial California mouse (Peromyscus californicus) to investigate how the effects of postvictory testosterone (T) release and winning experience individually mediate positive changes in future winning ability and antagonistic behavior. Male mice were castrated and implanted with T capsules to maintain basal levels of this hormone. We found that males form a robust winner effect if they win three separate territorial disputes and experience a single T surge roughly 45 min after each encounter. Meanwhile, males exhibit only an intermediate winner effect if they either 1) acquire three previous wins but do not experience a change in postvictory T or 2) acquire no previous wins but experience three separate T pulses. The results indicate that the effect of postvictory T must be coupled with that of winning experience to trigger the maximum positive shift in winning ability, which highlights the importance of social context in the development of the winner effect. At the same time, however, postvictory T and winning experience are each capable of increasing future winning ability independently, and this finding suggests that these two factors drive plasticity in antagonistic behavior via distinct mechanistic channels. More broadly, our data offer insight into the possible ways in which various species might be able to adjust their behavioral repertoire in response to social interactions through mechanisms that are unlinked from the effects of gonadal steroid action.

Species differences in the winner effect disappear in response to post-victory testosterone manipulations

Evolutionary processes can interact with the mechanisms of steroid hormone action to drive interspecific variation in behavioural output, yet the exact nature of these interactions is poorly understood. To investigate this issue, we compare the endocrine machinery underlying the winner effect (an ability to increase winning behaviour in response to past victories) in two closely related species of Peromyscus mice. Typically, after winning a fight, California mice (Peromyscus californicus) experience a testosterone (T) surge that helps enhance their future winning behaviour, whereas white-footed mice (Peromyscus leucopus) experience neither a T surge nor a change in subsequent winning behaviour. However, our results indicate that when the post-victory T response of male white-footed mice is phenotypically engineered to resemble that of California mice, individuals are capable of developing a strong and lasting winner effect. Moreover, this ‘induced’ winner effect in white-footed mice qualitatively matches the winner effect that develops naturally in California mice. Taken together, these findings suggest that white-footed mice have the physiological machinery necessary to form a robust winner effect comparable to that formed by California mice, but are unable to endogenously activate this machinery after achieving winning experiences. We speculate that evolutionary processes, like selection, operate on the physiological substrates that govern post-victory T release to guide divergence in the winner effect between these two species.

Deciding to win: interactive effects of residency, resources and 'boldness' on contest outcome in white-footed mice

Various environmental and social factors can bias who wins and who loses a fight, but less is known about how these factors interact with each other to affect contest outcome. We examined this issue in the white-footed mouse, Peromyscus leucopus, as males of this species illustrate great flexibility in aggressive and territorial tactics in the field and in the laboratory. We found that the effects of both residency status and resource abundance (food, water and cover from predators) increased winning ability; however, there was no interaction between these two effects. As such, the impacts of residency and resource abundance on winning might represent two distinct behavioural phenomena that manifest via different mechanisms. We also found that mice that urine-marked an open arena at a high frequency were more likely to win fights in resource-rich environments compared to resource-poor environments. Meanwhile, mice that urine-marked the same type of environment at a substantially lower frequency did not show this behavioural difference between contexts. Because urinary marking behaviour is allied with aspects of risk-taking behaviour and social status, this result implies that males integrate information about their relative ‘boldness’ with information from their environment to make context-appropriate tactical decisions about fighting. We speculate that our data illustrate real-time, decision-making processes that are a necessary component of conditional strategies used to optimize fitness.