The role of serotonin in the prefrontal cortex of the common marmoset

The aim of this thesis was to compare the behavioural effects of selective serotonergic lesions of the PFC using 5,7-dihydroxytryptamine, in a New World primate, the common marmoset (Callithrix jacchus), on two tests of prefrontal cortical function designed to measure the flexible control of inhibitory responding. First, the role of 5-HT in orbitofrontal cortex function was assessed using a serial discrimination reversal task in which monkeys have to repeatedly shift their responding between one of two visual stimuli. In contrast to controls, 5-HT-lesioned monkeys were impaired in their ability to reverse stimulus-reward associations, due to perseveration at the previously-correct stimulus. Second, the role of 5-HT in lateral PFC function was assessed using an attentional set-shifting task in which monkeys have to shift their attention between two perceptual dimensions of a compound visual stimulus. Despite lesioned monkeys showing perseverative responding when reversing a stimulus-reward association, the same monkeys were unimpaired in their ability to shift between higher-order dimensions or rules. Finally, two studies were undertaken to characterize the perseverative deficit both neurochemically and psychologically. Although selective orbitofrontal cortex dopamine lesions were without effect, selective 5-HT lesions of the orbitofrontal and lateral PFC induced perseveration, which was not due to learned avoidance or proactive interference. These findings suggest that PFC 5-HT (but not dopamine) is critical for flexible responding at the level of changing stimulus-reward contingencies, but is not essential for the higher-order shifting of attentional sets, thus highlighting the differential sensitivity of distinct prefrontally-mediated psychological functions to serotonergic modulation. Further characterization of the 5-HT systems involved in this deficit may reveal drug targets for the treatment of psychiatric disorders in which these abilities are impaired.EThOS - Electronic Theses Online ServiceGBUnited Kingdo