Electrophysiological studies have shown that mesostriatal dopamine (DA) neurons increase activity in response to unpredicted
rewards. With respect to other functions of the mesostriatal dopaminergic system, dopamine’s actions show prominent laterality
effects. Whether changes in DA transmission elicited by rewards also are lateralized, however, has not been investigated. Using
[11C]raclopride-PET to assess the striatal DA response to unpredictable monetary rewards, we hypothesized that such rewards would
induce an asymmetric reduction in [11C]raclopride binding in the ventral striatum, reflecting lateralization of endogenous dopamine
release. In 24 healthy volunteers, differences in the regional D2 ⁄ 3 receptor binding potential (DBP) between an unpredictable reward
condition and a sensorimotor control condition were measured using the bolus-plus-constant-infusion [11C]raclopride method. During
the reward condition subjects randomly received monetary awards while performing a ‘slot-machine’ task. The DBP between
conditions was assessed in striatal regions-of-interest and compared between left and right sides. We found a significant
condition · lateralization interaction in the ventral striatum. A significant reduction in binding potential (BPND) in the reward condition
vs. the control condition was found only in the right ventral striatum, and the DBP was greater in the right than the left ventral striatum.
Unexpectedly, these laterality effects appeared to be partly accounted for by gender differences, as our data showed a significant
bilateral BPND reduction in women while in men the reduction reached significance only in the right ventral striatum. These data
suggest that DA release in response to unpredictable reward is lateralized in the human ventral striatum, particularly in males.