Little is yet known about the regional neurochemical systems that influence learning in social contexts. So far, basic research in nonhuman animals [3] and human neuroimaging studies using drug challenges [4,5], as well as studies with individuals suffering from Parkinson’s disease [6,7,8] have delineated the dopamine system with a particular emphasis on the striatum as being a fundamental basic neurocircuitry underlying probabilistic reward-learning in humans. However, recent research has begun to probe theinvolvement of the striatum in more complex behaviors typically observed in repeated social interactions between two individuals. For instance, human neuroimaging studies investigating the neural correlates of repeated trust interactions have shown that positive social Title Loaded From File feedback such as reciprocated trust activates an individual’s striatum, whereas selfish, non-reciprocated trust leads to a decrease in striatal activity [1,2], for a review see [9]. Title Loaded From File Furthermore, activation in the striatum also predicts future trust decisions [10], suggesting that striatal activity might signal the rewards of positive social feedback and thereby guides future decisions. Thus, it appears that reward learning based on social outcomes (e.g., social approval, positive emotional responses and positive social feedback in repeated interactions) is coded similarly in reward circuitry as if feedback was based on non-social outcomes [11,12,13]. In sum, there is much reason to believe that a pharmacological manipulation of striatal dopamine modulates learning about others’ prosocial preferences by relying fundamentally on a basic probabilistic reward-learning mechanism. Striatal dopamine levels are dependent on the availability of the dopamine transporter (DAT) protein, as it reuptakes dopamine from the synaptic cleft into the pre-synaptic compartment after its release. Therefore, DAT is an important regulator of dopamine signaling, most primarily in the striatum, as it only occurs in lowDopamine and Learning about Others’ Prosocialityconcentrations in other areas of the brain [14]. There is substantial genetic variation in protein expression levels, and this variation is assumed to affect endogenous striatal dopamine levels. The most extensively studied gene variant in this context is the 40 base-pair variable number tandem repeat polymorphism of the dopamine transporter (DAT1 polymorphism) [15]. Basic neurobiological research has shown that the 9-repeat (9R) variant of the DAT1 23727046 polymorphism is associated with lower transporter protein expression than the 10R variant [16,17]. Neurochemical imaging research in humans reported a lower density of dopamine transporter in striatum of individuals who carry a 9/10R genotype (heterozygotes) compared to those who carry the 10/10R (homozygotes) genotype [18]. Hence, 9/10R genotype individuals are expected to have higher extrasynaptic striatal dopamine levels than 10/10R carriers [19,20,21,22]. Accordingly, functional imaging studies have consistently reported that 9/10R genotype carriers show greater activity in the striatum during processing of rewards compared to 10/10R carriers [19,20,21]. Data stemming from Parkinson’s disease patients who are treated with Ldihydroxy-phenylalanine (L-DOPA, a biochemical precursor of dopamine) suggest that the drug interacts with the DAT1 polymorphism in ways that are consistent with the above line of arguments. Patients who carry the 9/10R genotype are more likely to experience long t.Little is yet known about the regional neurochemical systems that influence learning in social contexts. So far, basic research in nonhuman animals [3] and human neuroimaging studies using drug challenges [4,5], as well as studies with individuals suffering from Parkinson’s disease [6,7,8] have delineated the dopamine system with a particular emphasis on the striatum as being a fundamental basic neurocircuitry underlying probabilistic reward-learning in humans. However, recent research has begun to probe theinvolvement of the striatum in more complex behaviors typically observed in repeated social interactions between two individuals. For instance, human neuroimaging studies investigating the neural correlates of repeated trust interactions have shown that positive social feedback such as reciprocated trust activates an individual’s striatum, whereas selfish, non-reciprocated trust leads to a decrease in striatal activity [1,2], for a review see [9]. Furthermore, activation in the striatum also predicts future trust decisions [10], suggesting that striatal activity might signal the rewards of positive social feedback and thereby guides future decisions. Thus, it appears that reward learning based on social outcomes (e.g., social approval, positive emotional responses and positive social feedback in repeated interactions) is coded similarly in reward circuitry as if feedback was based on non-social outcomes [11,12,13]. In sum, there is much reason to believe that a pharmacological manipulation of striatal dopamine modulates learning about others’ prosocial preferences by relying fundamentally on a basic probabilistic reward-learning mechanism. Striatal dopamine levels are dependent on the availability of the dopamine transporter (DAT) protein, as it reuptakes dopamine from the synaptic cleft into the pre-synaptic compartment after its release. Therefore, DAT is an important regulator of dopamine signaling, most primarily in the striatum, as it only occurs in lowDopamine and Learning about Others’ Prosocialityconcentrations in other areas of the brain [14]. There is substantial genetic variation in protein expression levels, and this variation is assumed to affect endogenous striatal dopamine levels. The most extensively studied gene variant in this context is the 40 base-pair variable number tandem repeat polymorphism of the dopamine transporter (DAT1 polymorphism) [15]. Basic neurobiological research has shown that the 9-repeat (9R) variant of the DAT1 23727046 polymorphism is associated with lower transporter protein expression than the 10R variant [16,17]. Neurochemical imaging research in humans reported a lower density of dopamine transporter in striatum of individuals who carry a 9/10R genotype (heterozygotes) compared to those who carry the 10/10R (homozygotes) genotype [18]. Hence, 9/10R genotype individuals are expected to have higher extrasynaptic striatal dopamine levels than 10/10R carriers [19,20,21,22]. Accordingly, functional imaging studies have consistently reported that 9/10R genotype carriers show greater activity in the striatum during processing of rewards compared to 10/10R carriers [19,20,21]. Data stemming from Parkinson’s disease patients who are treated with Ldihydroxy-phenylalanine (L-DOPA, a biochemical precursor of dopamine) suggest that the drug interacts with the DAT1 polymorphism in ways that are consistent with the above line of arguments. Patients who carry the 9/10R genotype are more likely to experience long t.
