| Popis: |
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. |
