UNIVERSITY OF AMSTERDAM – BRAIN AND COGNITIVE SCIENCE – COGNITIVE TRACK The roles of serotonin and dopamine in reactive and proactive aggression A literature thesis in partial fulfilment of the requirements for the degree of Master of Science Jonathan Krikeb, BSc, 10065180 12 June 2015 Supervisor: Co-assessor: dhr. prof. dr. C.K.W. de Dreu dhr. dr. M.P. Lebreton Krikeb, J., Serotonin and dopamine in predator-prey aggression Abstract: Aggression is often linked to violence but this is not a necessary connection. Aggression could also be motivating choices for economic-decision making. The question of what leads to aggression is what this paper will address as it discusses the bi-modal classification of aggression: proactive and reactive. These two classes will be linked to a new predator-prey research paradigm that separates the greed and its proactive tendencies, from the fear and its reactive actions. This, as well as a few other economic games, will be linked to the wide scope of research into aggressive violent behaviour, that is mostly based on clinical cases, as well as decision-making research that is founded on the idea that focuses on impulsive behaviour as it has been linked to aggression in the past. These past findings have also found correlations between serotonin hypoactivity, and also dopamine hyperactivity, in cases of irregular aggressive behaviour. We will attempt to establish how activities of the serotonergic and the dopaminergic circuitries parallel aggression in predator and prey type of interactions. 1 Krikeb, J., Serotonin and dopamine in predator-prey aggression Table of Contents 1. Introduction.......................................................................................................................................4 1.1. Aggressive behaviour.................................................................................................................4 1.2. Bi-modal classification of aggression.........................................................................................6 1.3. Aggression networks..................................................................................................................8 2. Experimental paradigms..................................................................................................................10 2.1. Aggressive behaviour in economic games...............................................................................10 2.2. The predator prey game..........................................................................................................11 2.2.1. Greed and calculated aggression in the predator............................................................14 2.2.2. PFC and goal-oriented behaviour....................................................................................14 2.2.3. Fear and reactive aggression in the prey.........................................................................16 2.2.4. Amygdala and fearful behaviour......................................................................................16 2.3. Aggressive behaviour in current research on neurotransmitters............................................18 2.4. Impulsive behaviour in experiments........................................................................................20 2.5. Experimental paradigms of impulsivity....................................................................................21 2.5.1. 5-CSRT..............................................................................................................................22 2.5.2. Go/no-go.........................................................................................................................22 2.5.3. SSRT.................................................................................................................................23 2.5.4. Reversal learning.............................................................................................................23 2.5.5. Delayed reward...............................................................................................................23 3. Serotonin.........................................................................................................................................23 3.1.1. Molecule..........................................................................................................................24 3.1.2. Different receptors in different brain regions..................................................................25 3.1.3. Tryptophan depletion......................................................................................................27 3.1.4. Tryptophan supplementation..........................................................................................28 2 Krikeb, J., Serotonin and dopamine in predator-prey aggression 3.1.5. Serotonin knockouts........................................................................................................28 3.1.6. Specific agonists/antagonists and neurotoxins................................................................29 3.2. Serotonin and impulsivity........................................................................................................29 3.3. Link between serotonin research to predator and prey behaviours........................................30 4. Dopamine........................................................................................................................................35 4.1.1. Molecule..........................................................................................................................35 4.1.2. Different receptors in different brain regions..................................................................35 4.1.3. Parkinson’s and L-dopa....................................................................................................37 4.1.4. Other manipulations to dopamine..................................................................................37 4.2. Dopamine and impulsivity.......................................................................................................38 4.3. Link between dopamine research to predator and prey behaviours.......................................38 5. Interactions between serotonin and dopamine...............................................................................39 6. Discussion........................................................................................................................................40 3 Krikeb, J., Serotonin and dopamine in predator-prey aggression 1. Introduction An attack to gain more resources by someone who has an abundance of them does not have the same motivation as the defensive reaction of the prey, in this same scenario, that defends its limited resources. In this sort of predator against prey interaction, two types of aggression come into play: proactive and reactive. Reactive aggression has been widely studied, often in context of impulsive aggression, while the literature on proactive aggression is more scarce. In light of the research into the motives behind these behaviours, and how this is reflected in terms of neurotransmitters, this paper will follow past studies and look at how the key neurotransmitters serotonin and dopamine interact in these two different types of aggression, namely predator and prey. 1.1. Aggressive behaviour Aggression traditionally requires a conflict between at least two parties that may compete for the same object, physical or otherwise (Nelson & Trainor, 2007).Since aggression and violence often go hand-in-hand, the results of aggressive behaviour often lead to damage, which is often physical, and therefore aggression is dangerous and not always the best choice in conflict circumstances. It does have an evolutionary role in food, or mate, acquisition, or protection, as well as inner motivations such as fear, greed, anger or even pleasure. When these motives lead to aggressive acts that hurt, or injure others, then we consider aggression as unaccepted in our current human society – war or criminal acts such as robbery or battery (de Almeida, Ferrari, Parmigiani, & Miczek, 2005). There is a wide selection of literature available on aggression, much of it is composed of psychological research focusing on clinical and criminal cases such as: workplace aggression (Hills & Joyce, 2013; Piquero, Piquero, Craig, & Clipper, 2013; S. F. Smith & Lilienfeld, 2013), domestic aggression (George et al., 2001; Soler, Vinayak, & Quadagno, 2000), alcohol and drug related (Anholt 4 Krikeb, J., Serotonin and dopamine in predator-prey aggression & Mackay, 2012; Badawy, 2003; de Almeida et al., 2005; George et al., 2001; Gowin, Swann, Moeller, & Lane, 2010; Skara et al., 2008), and arson (Linnoila, Virkkunen, & Scheinin, 1983). All this research shows how ingrained in human society aggression is and how destructive it could get, thus necessitating a deeper understanding of the motives behind it. In order to better understand aggression and its motives, different classification systems were established. In this paper, as the introduction suggests, we will focus on a binary classification system. Two other systems were suggested in previous studies as well. First, as described both by Siegel and Victoroff (2009) and Umukoro, Aladeokin, and Eduviere (2013) where they divide aggression into seven separate motivations it may originate from: fear -induced, maternal, irritable, inter-male, sex-related, predatory, and territorial.