Novel mechanisms for neuroendocrine regulation of aggression

Abstract

In 1849, Berthold demonstrated that testicular secretions are necessary for aggressive behavior in roosters. Since then, research on the neuroendocrinology of aggression has been dominated by the paradigm that the brain receives gonadal hormones, primarily testosterone, which modulate relevant neural circuits. While this paradigm has been extremely useful, recent studies reveal important alternatives. For example, most vertebrate species are seasonal breeders, and many species show aggression outside of the breeding season, when gonads are regressed and circulating testosterone levels are typically low. Studies in birds and mammals suggest that an adrenal androgen precursor—dehydroepiandrosterone (DHEA)—may be important for the expression of aggression when gonadal testosterone synthesis is low. Circulating DHEA can be metabolized into active sex steroids within the brain. Another possibility is that the brain can autonomously synthesize sex steroids de novo from cholesterol, thereby uncoupling brain steroid levels from circulating steroid levels. These alternative neuroendocrine mechanisms to provide sex steroids to specific neural circuits may have evolved to avoid the “costs” of high circulating testosterone during particular seasons. Physiological indicators of season (e.g., melatonin) may allow animals to switch from one neuroendocrine mechanism to another across the year. Such mechanisms may be important for the control of aggression in many vertebrate species, including humans.

Introduction

One of the more important and intensely studied social behaviors exhibited by animals is aggression [19], [20], [75], [109]. Aggression is a complex suite of behaviors that is displayed by virtually all organisms and serves a wide range of adaptive functions. In general, aggressive behavior is exhibited when the interests of two or more individuals are in conflict, typically involving critical limited resources (e.g., food, territories, and mates). Often, a submissive posture displayed by one animal avoids the need for physical aggression. Additionally, animals may engage in threat displays or ritualized combat, in which dominance is established without physical harm. If such displays are ineffective, however, physical aggression can result. In some cases, animals may fight simply to ascertain dominance status [64].

Aggression is a notoriously nebulous concept that has been defined and categorized in a multitude of ways. Aggression has traditionally been defined as overt behavior with the intention of inflicting physical damage upon another individual or “goal entity” [72]. A commonly employed classification scheme was described by Moyer, who divided aggression into specific subtypes based on differences in social conditions in which the behavior was observed [72]. These subtypes of aggression include: predatory aggression, inter-male aggression, fear-induced aggression, irritable aggression, maternal aggression, territorial aggression, and instrumental aggression. The primary tenet of Moyer’s classification system is that, although these different forms of aggression share behavioral features, the environmental factors eliciting these behaviors and their biological substrates differ markedly. More recently, a simplified classification scheme has been suggested [9] in which aggression is divided into offensive and defensive aggression. Behaviors used in attack are referred to as offensive, whereas defensive aggression does not involve an active approach to the opponent. This latter classification system provides a useful framework with which to identify and describe aggressive behavior across many species.

Aggressive behavior has been studied under a wide range of experimental conditions. It is often difficult, therefore, to compare results across studies. A relatively large number of experimental models have been developed to test aggression (e.g., electric shock-induced aggression and conditioned aggression). One of the prevalent models for assessing offensive aggression has been the resident-intruder model. This test is intended to simulate territorial aggression and involves introducing an “intruder” into the territory of an experimental animal, and the amount and duration of aggressive behavior (e.g., chases, attacks, and bites) are recorded in a timed test. The neutral arena model is a test in which two animals are placed in a novel “neutral” environment, and the amount of aggression directed towards each animal is recorded. The neutral arena model allows assessment of the development of a dominance relationship.

It is important to consider other issues, such as the time of behavioral testing (e.g., day vs. night). Rodents are typically nocturnal and display more aggressive behavior during the night. In contrast, many birds and primates are diurnal, and behavioral testing is performed during the day. Moreover, given the robust effects of melatonin on aggression (see below), time-of-day and day length (photoperiod) effects might be substantial but greatly underappreciated. In many publications, the day length for laboratory-housed animals is either not reported or invariant (typically 12 h light: 12 h darkness). Endocrine regulation of aggression may differ under other day lengths.

A majority of the research on the physiology of aggression has used laboratory rodent models, particularly inbred strains of rats and mice [6], [13], [14], [26], [132]. These models have provided, and continue to provide, important insights into the mechanisms of aggression. However, the mechanisms mediating aggression can differ across taxa [144], and comparative studies shed light on general principles and the evolution of endocrine mechanisms. Here, we will review findings from various taxa, with an emphasis on birds and rodents, to draw attention to common themes as well as noteworthy differences in the neuroendocrine regulation of aggression.