The neuropsychopharmacology of reversal learning

Nilsson, Simon (2013) The neuropsychopharmacology of reversal learning. Doctoral thesis (PhD), University of Sussex.

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Reversal learning deficits are a feature of many neuropsychiatric disorders, most
notably schizophrenia. These deficits could be due, in part, to altered ability to dissipate
either or both associations of previous positive (perseverance) and negative (learned
non-reward) valence. Studies reported in this thesis developed an egocentric maze task
and a visuospatial operant task for separate assessments of spatial reversal learning,
perseverance and learned non-reward in mice. These tasks were subsequently used to
assess the cognitive causes for altered performance after manipulations to brain systems
recognised to be involved in reversal learning and relevant for human psychopathology,
with a specific focus on schizophrenia.

NMDA receptor (NMDAr) antagonism through acute phencyclidine did not
affect reversal learning in the operant task, but caused general impairments in the maze
task. Orbitofrontal (OFC) lesioned mice showed perseverative impairments in the
operant task. Mice treated with the 5-HT2C receptor (5-HT2CR) antagonist SB242084
and 5-HT2CR KO mice showed facilitated reversal learning and decreased learned nonreward in the operant task. In the maze task, SB242084 decreased perseverance but increased learned non-reward, while 5-HT2CR KO mice showed perseverance and
discrimination learning deficits. The final experimental chapter investigated the effect of SB242084 on touch-screen visual reversal learning in the rat. SB242084 retarded
learning in this task.

These studies demonstrate that previously non-reinforced associations can be of
considerable importance in tasks of cognitive flexibility. The studies also show that the
NMDAr, the 5-HT2CR, and the OFC, are involved in reversal learning and can modulate
mechanisms related to both perseverance and learned non-reward. Moreover, in reversal
learning, few effects of manipulations affecting PFC-functioning, or activity at the
NMDAr and 5-HT2CR, generalise across the procedures in the visuospatial, egocentric
spatial, and visual domains.

Item Type: Thesis (Doctoral)
Schools and Departments: School of Psychology > Psychology
Subjects: B Philosophy. Psychology. Religion > BF Psychology > BF0309 Consciousness. Cognition Including learning, attention, comprehension, memory, imagination, genius, intelligence, thought and thinking, psycholinguistics, mental fatigue
Depositing User: Library Cataloguing
Date Deposited: 23 Jun 2013 10:52
Last Modified: 10 Sep 2015 14:57

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