Serotonin at the level of the amygdala and orbitofrontal cortex modulates distinct aspects of positive emotion in primates.

Impaired top-down regulation of the amygdala, and its modulation by serotonin (5-HT), is strongly implicated in the dysregulation of negative emotion that characterizes a number of affective disorders. However, the contribution of these mechanisms to the regulation of positive emotion is not well understood. This study investigated the role of 5-HT within the amygdala and the orbitofrontal cortex (OFC), on the expression of appetitive Pavlovian conditioned emotional responses and their reversal in a primate, the common marmoset. Its effects were compared to those of the amygdala itself. Having developed conditioned autonomic and behavioural responses to an appetitive cue prior to surgery, marmosets with excitotoxic amygdala lesions failed to display such conditioned autonomic arousal at retention, but still displayed intact cue-directed conditioned behaviours. In contrast, 5,7-DHT infusions into the amygdala, reducing extracellular 5-HT levels, selectively enhanced the expression of appetitive conditioned behaviour at retention. Similar infusions into the OFC, producing marked reductions in post-mortem 5-HT tissue levels, had no overall effect on autonomic or behavioural responses, either at retention or during reversal learning, but caused an uncoupling of these responses, thereby fractionating emotional output. These data demonstrate the critical role of the amygdala in the expression of appetitive autonomic conditioning, and the region-selective contribution of 5-HT in the amygdala and OFC, respectively, to the expression of conditioned behaviour and the overall coordination of the emotional response. They provide insight into the neurochemical mechanisms underlying the regulation of positive emotional responses, advancing our understanding of the neural basis of pathologically dysregulated emotion.