Serotonin and aggressive behavior in rodents and nonhuman primates: Predispositions and plasticity

doi:10.1016/j.ejphar.2005.10.002

European Journal of Pharmacology

Volume 526, Issues 1–3, 5 December 2005, Pages 259-273

https://doi.org/10.1016/j.ejphar.2005.10.002 Get rights and content

Abstract

This review analyzes psychosocial and genetic determinants of aggressive behavior in rodents and nonhuman primates and the role of the serotonin (5-HT) system on aggressive behaviors in order to trace possible evolutionary common origins between psychopathological and adaptive forms of aggression. Studies in primates suggest that deficit in serotonin activity, as indicated by the levels of the cerebrospinal fluid (CSF) serotonin major metabolite 5-hydroxyindoleacetic acid (5-HIAA) correlates with impulsive and aggressive behavior. It is possible that CSF 5-HIAA reflects the prevailing serotonergic tone and may be related to an aggressive trait. Superimposed on this tone are phasic serotonin changes that may be related to the inhibition of aggressive acts. Genetic factors determine aggressive behaviors as demonstrated by classic selection and strain comparison studies. Manipulations of genes targeting 5-HT receptors, transporters and enzymes can influence aggression. Some of these genes related to the serotonin transporter (5-HTT) and the monoamine oxidase A (MAO-A) show a polymorphism that may predispose, under specific environmental conditions, certain individuals to display pathological forms of aggression.

Section snippets

Adaptive and pathological forms of aggressive behaviors

Impulsive–hostile–injurious violent outbursts differ fundamentally from the premeditated instrumental calculating attacks in their extreme forms (Vitiello and Stoff, 1997), although many forms of aggressive behavior represent a mixture of both forms, proactive and reactive. In functional terms, it is possible to distinguish between two broad categories of adaptive aggression: one concerned with competition for resources (competitive aggression) and the other concerned with protection of self or

Aggression in rodents

In mice the social organization may vary, ranging from exclusive male territoriality to relative territorial dominance with despotic structure, depending on different socio-ecological conditions. Under natural and seminatural conditions, house mice live in small reproductive units (demes, Berry, 1981) consisting of a dominant male who sires virtually all the litters, one or several breeding females with their offspring, and occasionally some subordinate males (Crowcroft and Rowe, 1963, Reimer

Aggression in Old World monkeys

One interesting aspect of most nonhuman primates is their sociability and the complexity of the social organization. In particular, various Old World monkeys demonstrated that the social organization is based on a complex equilibrium of social relations in which relatedness, coalitions, alliances and hierarchies play a major role (Smuts, 1987). Such an equilibrium is often based and regulated by aggressive acts, postures and displays. Although living in groups could potentially favor the

The neurobiology of aggression: the 5-HT deficiency trait. Is brain serotonin activity linked to trait or to state aggression or both?

Brain 5-HT more than any other neurotransmitter has been implicated in the neural control of expressing aggressive behavior (Miczek et al., 1995). The wealth of literature on the relationship between aggression and serotonin continues to grow despite the fact that the first reports that proposed such a link date back about four decades (Maas, 1962, Garattini et al., 1967, Giacalone et al., 1968, Valzelli, 1981).The approaches to investigate 5-HT involvement in aggression, derive from different

5-HT, genes and aggression. Interaction between genes and environment

A significant portion of individual differences in aggressive behavior has been traced to genetic inheritance. For several decades animal research has addressed this topic by using mice and rats as animal models for aggression. Initial reports on genetic differences of male aggressive behaviors in mice were based on strain comparisons (Scott, 1942). Since then, a large number of studies have investigated aggressive behaviors in inbred and outbred strains of mice, recombinant lines or selected

Conclusions

We have focused on aggressive behavior in two phylogenetic groups: rodents and nonhuman primates. Despite clear differences in species-typical aggressive behaviors, in terms of behavioral patterns, motivations, triggering stimuli, behavioral biologists still consider the importance of emphasizing continuities in adaptive functions of aggressive behaviors across rodents and primates. This approach is important since it characterizes possible homologies with human aggression, and it traces the

Acknowledgements

We acknowledge financial support by the grant RBNE01SZB4 from the FIRB/MIUR and the grant I/R/351/02 from ASI. We would like to thank S. Suomi for his valuable comments on an early draft of the manuscript.

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Aggressive and submissive behaviours are commonly assumed to represent two extremes of a single personality trait, often labelled ‘aggressiveness’. However, most studies focus exclusively on submissive behaviour elicited by conspecific aggression, and on rates at which aggressive and submissive behaviours are expressed, without considering either unprovoked submissive behaviour, or the intensity of the actions themselves. Utilizing a long-term data set spanning 27 years of dyadic agonistic interactions among spotted hyaenas, Crocuta crocuta, including counts and intensities of all unprovoked acts of aggressive and submissive behaviour, we assessed consistency within individuals in these behaviours. We found that counts of acts of both aggression and submission performed by adult female hyaenas varied with context, that neither measure was consistent within individuals over time and that both were strongly affected by social rank, suggesting that neither of these rate measures represent personality traits. Although rank influenced the intensity of submissive acts, intensity of aggressive acts did not vary with rank. Intensities of aggressive and submissive acts also varied with context, but both were consistent within individual females regardless of age, suggesting that both intensity measures may represent personality traits. We found no significant correlation between individual lifetime averages of intensities of aggressive and submissive behaviour, supporting the hypothesis that these may represent different traits rather than opposite ends of a single spectrum. Lifetime rates at which females performed acts of aggression and submission were uncorrelated with fitness, but analysis of the average intensity of aggressive or submissive acts performed by adult female hyaenas suggests that lifetime reproductive success may be lower at both ends of the spectrum of behavioural intensity than in its centre after controlling for rank, suggesting the action of stabilizing selection.
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Aggression is observed in practically all animal species, including humans. Such evolutionary conservation underscores the importance of this behavior for animals’ fitness and survival. Animals fight to defend territory, acquire food, compete for mates, and to protect their offspring. However, despite decades of research, our knowledge of neurobiological underpinnings of aggressive behavior is still far from complete. Serotonergic system has been most consistently linked to both adaptive and pathological forms of this behavior. For a long time, a prevailing hypothesis was that serotonin exerts inhibitory effect on aggression. However, ample evidence has shown that such a view may be overly simplistic and that no one-to-one relationship is likely to exist between the serotonin and aggressive behavior. In this chapter, we review the complex interplay between this iconic neurotransmitter and aggression.

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^☆: PFF, SP and KAM contributed equally to the paper.

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ReviewSerotonin and aggressive behavior in rodents and nonhuman primates: Predispositions and plasticity☆

Abstract

Section snippets

Adaptive and pathological forms of aggressive behaviors

Aggression in rodents

Aggression in Old World monkeys

The neurobiology of aggression: the 5-HT deficiency trait. Is brain serotonin activity linked to trait or to state aggression or both?

5-HT, genes and aggression. Interaction between genes and environment

Conclusions

Acknowledgements

Aggress. Behav.

Physiol. Behav.

Psychoneuroendocrinology

Psychiatry Res.

Psychiatry Res.

Brain Res.

J. Neurosci. Methods

Eur. J. Neurosci.

Neuropsychopharmacology

Neuropsychopharmacology

Physiol. Behav.

Physiol. Behav.

Physiol. Behav.

Biochem. Pharmacol.

Prog. Neuropsychopharmacol. Biol. Psychiatry

Ethol. Sociobiol.

Anim. Behav.

Neurosci. Res.

Behav. Brain Res.

Life Sci.

Motivational systems of agonistic behavior in muroid rodents: a comparative review and neural model

Aggress. Behav.

The Behavioural Biology of Aggression

The Rat. A Study in Behavior

Influence of females on conflict among wild rats

J. Zool.

Serotonin transporter gene variation is associated with alcohol sensitivity in rhesus macaques exposed to early-life stress

Alcohol., Clin. Exp. Res.

The utility of the non-human primate; model for studying gene by environment interactions in behavioral research

Genes Brain Behav.

Behavioral response to novel objects varies with CSF monoamine concentrations in rhesus monkeys

Soc. Neurosci. Abstr.

Early experience and serotonin transporter gene variation interact to influence primate CNS function

Mol. Psychiatry

Aggression. Its Causes, Consequences and Control

Role of dominant male rhesus monkey in response to external challlenges to the group

J. Comp. Physiol. Psychol.

Modification of aggression through socialization and the special case of adult and adolescent male rhesus monkey (Macaca mulatta)

Am. J. Primatol.

Population dynamics of the house mouse

Symp. Zool. Soc. Lond.

Neurocognitive models of aggression, the antisocial personality disorders, and psychopathy

J. Neurol. Neurosurg. Psychiatry

Attack and defensive behavior in the albino rat

Anim. Behav.

Social dominance and individual aggressiveness

Aggress. Behav.

Differentiating types of attack and defence in rodents

Sequence analysis of social behaviour illustrating the actions of two antagonists of endogenous opioids

Prog. Clin. Biol. Res.

House Mouse Aggression. A Model for Understanding the Evolution of Social Behaviour

The reproductive ecology of the house mouse

Q. Rev. Biol.

Insights into the neurology of impulsive behavior from serotonin to receptor knockout mice

Ann. N.Y. Acad. Sci.

Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A

Science

A developmental-genetic analysis of aggressive behavior in mice. I. Behavioral outcomes

J. Comp. Psychol.

Limbic corticostriatal systems and delayed reinforcement

Ann. N.Y. Acad. Sci.

Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA

Science

Role of genotype in the cycle of violence in maltreated children

Science

Serotonin transporter gene polymorphism and neurobehavioral development in rhesus monkey neonates

Mol. Psychiatry

Matriline membership and male rhesus reaching high ranks in the natal troop

Why do adult male and female rhesus monkeys affiliate during the birth season?

Interactions and relationships between groups

Review
Serotonin and aggressive behavior in rodents and nonhuman primates: Predispositions and plasticity☆