The Neuroanatomical and Neuropharmacological Bases of Aggression

Cognition and Emotion / PSY 205

The Neuroanatomical and Neuropharmacological Bases of Aggression

Aggression is the term most commonly used to describe when animals threaten, bite and/or kill one another (Panskepp, 1998). Although this behaviour is not universal or one-dimensional, with many invertebrates and almost all vertebrates displaying aggression, including humans. Where does this behaviour originate? The scientific community once believed aggression to be a solely socially learned behaviour, but the use of Electrical Stimulation of the Brain (ESB) in animals – inducing aggressive behaviour – has disproved this theory. ESB is a procedure whereby subjects’ brains are excited in a specific area through the use of an electrode. The area excited can be very specific, allowing precise mapping of suspected areas that control certain functions. Essentially, a small current excites the nearby neurons, and the observers are able to note the subject’s reaction (Panskepp 1998). Experiments involving this technique illustrated that aggressive behaviour could be induced solely by ESB, without the help of any other stimulus (Panskepp 1998). ESB has been quite successful in providing information about physiological components of aggression in animals; however using it in human subjects throws up various ethical concerns and specific cognitive factor difficulties. While experimentation on animals cannot fully explain why humans exhibit and inhibit aggression, it can provide clues as to the primitive neurological basis of the subject (Panskepp 1998). This paper will explore the neuroanatomical bases of aggression, including the three different aggression brain circuits, as well as the neuropharmacological bases of aggression, including the role of the 5-HT, norepinephrine and testosterone.

Viewing the subject firstly from a neuroanatomical standpoint, there are three main structures which mediate aggression – the amygdala, the hypothalamus and the periaqueductal gray (PAG); all three are affected by input from many other brain structures. It has been argued that there are three ‘types’ of aggression to match the three structures’ circuits listed above. These are the ‘predatory’ (quiet-biting) circuit, the affective attack (RAGE) circuit, and the intermale aggression circuit. The individuality of these circuits can be seen in the observable different behaviours involved in each. When an animal exhibits affective attack aggression, it becomes autonomically aroused and may display behaviours such as hissing, growling and piloerection. However, when an animal is undergoing predatory aggression, it does not display any autonomical arousal, instead exhibiting methodological stalking and well-directed pouncing (Flynn, 1976). Experiments, often including the use of ESB, have revealed the distinctiveness of the neural anatomy of these systems. In 1990, Siegel and Brutus found that when the dorsolateral hypothalamus of the cat is activated, predatory aggression could be observed. This was contrasted by the activation of the ventrolateral and medial hypothalamus, which frequently resulted in affective attack aggression. These findings follow on from those of Bandler in 1988, who showed that activation of the ventral PAG leads to predatory aggression, whilst the activation of the dorsal half of the PAG led to affective attack aggression. Further research evidence suggests that the predatory aggressive circuit overlaps the SEEKING circuit, while the affective attack circuit is more associated with the RAGE circuit. However, this contrasts with the intermale aggressive circuits, which seems to be linked with the sexual control systems.

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When focusing on predatory aggression, we can see SEEKING and predation are stimulated from similar overlapping brain areas, both invoking self-stimulation. This “helps to coax animals and humans to move energetically from where they are to the places where they can find and consume the fruits of the world” (Panskepp, 1998). Panskepp actually suggests that self-stimulation and predatory aggression may be just two different behavioural expressions of seeking instincts that come from homologous systems in the brains of different species (1998). Indeed, pharmacologically, quiet-biting aggression and self-stimulation are both suppressed by dopamine or L-Dopa. Dopamine – or the artificial L-Dopa – is a neurotransmitter that is thought to be involved in the SEEKING circuit. Which brain systems are involved in the SEEKING system? When stimulating this response using ESB, the ascending dopaminergic circuits are most often looked at. Specifically, the major pathway of this system travels through the ventrolateral regions of the diencephalons, which includes the medial forebrain bundle (MFB) of the lateral hypothalamus (Panskepp, 1998).

In contrast, the affective attack aggression is closely associated with the RAGE circuit. This circuit is arranged hierarchically, being composed mainly of the amygdala hypothalamus and the PAG. This means that the higher areas – such as the amygdala – are tied to the functioning of the lower areas, but the amygdala can function in the absence of the PAG, for instance by lessoning, but contains behaviours that are unable to be expressed (DeMolina & Hunsperger, 1962). This suggests that the PAG is the primitive source of instinctive aggression; however, in primates, it accepts input from the higher areas, such as the frontal cortex, the orbitoinsular cortex – especially the insular area – and the medial hypothalamus. The input of the frontal cortex includes information from areas concerned with rewards and visual areas involved with prominent objects in the visual field. The input from the senses, especially pain and hearing, may converge in the orbitoinsular cortex. The medial hypothalamus is also involved in energy homeostasis and sexual issues, possibly influencing aggression in this area (Panskepp 1998). However, not only does the PAG accept input from higher brain areas, but also it is connected to lower areas. These include the vestibular complex, nucleus of solitary tract, and the amine cell groups, involved (respectively) in bodily orientation, the collection of the current internal state and all behaviour in general (Panskepp, 1998).

Intermale aggression can be viewed as different from the other types of aggression discussed above because it is mostly tied to reproduction, including territory defending and competing for females behaviours. This type of aggression is more common in males, as its title suggests. However, males are prevented from attacking females, at least in the primate world, through the release of pheromones by the females (Carlson, 1998). This process is controlled by the medial amygdala, a process seen by the fact that it is integrating an olfactory stimulus and aggression regulation.

As stated in the introduction, other components that are necessary to consider when trying to understand the neural bases of aggression are the neuropharmacological factors, including neurotransmitters – such as 5-HT and norepinephrine – and hormones such as testosterone. Neurotransmitters serve “either to activate or prevent the ‘firing’ of downstream neurons” (Berman, Tracy & Coccaro, 1997). 5-HT is a neurotransmitter that is thought to have some influence on aggressive behaviour. Coccaro asserts that, in general, 5-HT serves to modulate or constrain ongoing behaviour, preventing extreme behaviour, so it follows that a deficiency of 5-HT or a similar substance could increase a subject’s tendency towards extreme behaviours, such as arson, suicide or extreme aggression (Coccaro, 1992). Increased activity of serotonergic synapses can inhibit aggression, giving a reason why serotonergic-based drugs can be used to help control some cases of aggressive personalities. 5-hydroxyindoleacetic acid (5-HIAA) is a major metabolite of 5-HT, which can be found in cerebrospinal fluid, showing that the density of 5-HIAA can be an indicator of the level of serotonergic activity. Higley et al (1996) conducted a controlled experiment where the levels of 5-HIAA of rhesus monkeys were recorded, and their behaviour objectively noted. A link was established between monkeys with depressed lower levels of 5-HIAA and a pattern of risk-taking (aggressive behaviour towards larger, older monkeys). A follow up study four years later showed that the survival rates of the higher levelled 5-HIAA monkeys was still at 100%; however, the lower, more (generally) aggressive monkeys had a mortality rate of 54% - that is, 46% of the monkeys had died. Similarly, Sidou (cited in Panskepp, 1998) discovered that mice born without 5-HT1B receptors attacked an intruder more quickly and with more intensity than those with normal receptors. This all suggests that some animals, at least, with a deficiency of 5-HT – or a similar neurotransmitter – show more aggressive behaviour of this type.

However, the situation may not be as straightforward as a simple causal link. Brunner et al. (1993) found a hyperaggressive Dutch family with a rare mutation of the gene that codes for monoamine oxidase type A, a chemical that, amongst other actions, breaks down serotonin. This could, however, be explained by the fact that the gene mutation may have inhibited or accelerated the action of other aggression systems. Another study by Simeon et al. (1992) showed that the levels of 5-HT in self-mutilating subjects was not particularly different from control subjects. Again, this could be countered by regarding self-mutilation not as an aggressive action, but one of a thousand others. Indeed, Berman, Tracy and Coccaro (1997) pointed out potential flaws with these experiments’ subject sizes possibly being too limited, their comparison groups not being controlled correctly, and there being methodological issues with the experiments’ systems. Another neurotransmitter that is widely thought to affect aggression is norepinephrine (NE). Gerra et al. (1997) conducted an experiment in which the main metabolite of NE, 3-methoxy-4-hydroxyphenylglycol (MHPG) was recorded in the cerebrospinal fluid of men who exhibited aggression within the normal range. It was found that the subjects with high-normal aggression had higher levels of NE than the men with low-normal aggression. It was postulated that NE modulates the quantity and qualities of aggressive states, through its stimulatory effects on testosterone secretion; however, it was noted that aggression might cause an aspecific stress condition that could elevate NE levels.

Hormones – such as testosterone – have classically been implicated in aggression, but their relationship (if any such relationship does exist) is as least as complicated as that between neurotransmitters and aggression. Factually, testosterone (being the most researched aggression-hormone) is produced in the hypothalamus-pituitary-gondal axis (Borod, 2000). Many studies have suggested a positive correlation between testosterone and aggression (Beeman, 1947). Early androgenization (sic) during early development modifies the brain to stimulate development of testosterone, which in turn is thought to sensitise neural circuits that facilitate intermale aggression (Carlson, 1998). Delville, Mansour and Ferris (1996) postulated that the facilitating of aggression through testosterone occurs by the modulation of arginine-vasopressin (AVP) receptors in the hypothalamus. To test this theory, an experiment was conducted where golden hamsters were castrated, with one half later treated with testosterone, and the other half being a control. The AVP receptors in the ventrolateral hypothalamus disappeared in those left untreated (control group), but in the test group, the receptors were still observed. In a follow-up experiment, a small quantity of AVP was injected directly into the ventrolateral hypothalamus. The test subjects showed acceleration in the onset of offensive aggression, whilst the control group did not. It must be noted that, despite this strong evidence for the involvement of testosterone in aggression, other controlled experiments have consistently failed to show any direct or indirect correlation.

In summary, the neuroanatomical and neuropharmacological bases of aggression are highly contentious topics. This can be put down not only to the large number of well-conducted experiments and studies that have arrived at opposing conclusions, but also due to the very sensitive often-political nature of the topic. Responsibility being taken away from the transgressor of a crime is controversial, and it is often very contentious to describe, for instance, the cause of violent crime as being ‘merely’ biological. It can be argued that this can only be a ‘good thing’ for the topic area, as further there is no worse fate than can befall a scientific question than pure apathy. It was beyond the realms of this essay to look at the cognitive, developmental, social and emotional factors that can contribute to aggression, and this is where the whole answer will lie, in the view of this paper. In conclusion:

The most broadly destructive kinds of human aggression – wars between nations and competing cultural groups, as well as many violent crimes – do not directly arise from brain circuits … these are instrumental acts that arise from the wilful activities of humans.

Panskepp, 1998.

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Bibliography

Bandler, R. (1988) Brain mechanisms of aggression as revealed by electrical and chemical stimulation: Suggestion of a central role for the midbrain periaqueductal gray region. In Progress in Psychobiology and Physiological Psychology 14, Epstein, A.N. & Morrison, A.R. (Eds.) pp 67-154, San Diego: Academic Press.

Beeman, E.A. (1947) The effect of male hormone on aggressive behaviour in mice. Physiological Zoology 20 pp 373-405.

Berman, M.E., Tracy, J.I. & Coccaro, E.F. (1997) The Serotonin Hypothesis Revisited. Clinical Psychology Review 17(6)

Borod, J. (2000) Neuropsychology of Emotion, Oxford: Oxford University Press.

Brunner, H.G., Nelen, M., Breakfield, X.O., Ropers, H.H., van Oost, B.A. (1993) Abnormal Behaviour associated with a Point Mutation in the Structure Gene for Monoamine Oxidase A. Science 262 pp 578-580.

Carlson, N.R. (1998) Physiology of Behaviour. London: Allyn & Bacon.

Carlson, N.R. (1995) Foundations of Physiological Psychology (3rd Ed.) Boston: Allyn and Bacon.

Carter, C.S. (1998) Neuroendocrine Perspectives on Social Attachment and Love. Psychoneuroendocrinology 23(8), 779-818.

Carter, C.S., DeVries, A.C., Getz, L.L. (1995) Physiological Substrates of Mammalian Monogamy: The Prairie Vole Model. Neuroscience and Behavioural Reviews, 19(2), 303-314.

Coccaro, E.F. (1992) Impulsive aggression and central serotonergic system function in humans: An example of a dimensional brain-behaviour relationship. International Clinical Psychopharmacology 7, pp 3-12.

DeMolina, A.F., Hunsperger, R.W. (1962) Organization of the subcortial system governing defence and flight reactions in the cat. Journal of Physiology 160, pp 200-213.

Deville, Y., Mansour, K.M., Ferris, C.F. (1996) Testosterone facilitates aggression by modulating vasopressin receptor in the hypothalamus. Physiology and Behaviour 60(1), pp 25-29.

Flynn, J.P. (1976) Neural basis of threat and attack. In Biological foundations of psychiatry, Grenell, R.G., Abau, S.G. (Eds.) pp 275-295. New York, Raven Press.

Freud, S. (1961) Civilizations and its Discontents. New York: W.W. Norton & Co.

Gerra, G., Zaimovic, A., Avanzini, P., Chittolini, B., Giucastro, G., Caccavari, R., Palladino, M., Maestri, D., Monica, C., Delsignore, R., Brambilla, F. (1997) Psychiatric Research 66, pp 33-43.

Higley, J.D., Mehlman, P.T., Poland, R.E., Taub, D.M., Vickers, J., Suomi, S.J., Linnoila, M. (1996) CSF testosterone and 5-HIAA correlate with different types of aggressive behaviour. Biological Psychiatry 40, pp 1067-1082.

Kalat, J.W. (1998) Biological Psychology (6th Ed.) Belmont: Wadsworth.

Nelson, E.E., Panskepp, J. (1998) Brain Substrates of Infant-Mother Attachment: Contributions of Opioids, Oxytocin and Norepinephrine. Neuroscience and Biobehavioral Reviews 22(3), 437-452.

Panskepp, J. (1998) Affective Neuroscience. Oxford: Oxford University Press.

Siegel, A., Brutus, M. (1990) Neural substrates of aggression and rage in the cat. In Progress in psychobiology and physiological psychology 13, Epstein, A.N., Morrison, A.R. (Eds.) pp 135-235. San Diego: Academic Press.

Simeon, D., Stanley, B., Frances, A., Mann, J.J., Winchel, R., Stanley, M. (1992) Self-mutilation in personality disorders: Psychological and Biological correlates. American Journal of Psychiatry 149, pp 221-226.