Investigating the effects of dopamine and 3’, 5’-cyclic adenosine monophosphate-regulated neuronal phosphoprotein, 32 kDa (DARPP-32) deletion on adaptive reward-based learning and performance

Mawer, David (2016) Investigating the effects of dopamine and 3’, 5’-cyclic adenosine monophosphate-regulated neuronal phosphoprotein, 32 kDa (DARPP-32) deletion on adaptive reward-based learning and performance. Doctoral thesis (PhD), University of Sussex.

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Abstract

Dopamine and 3',5'-cyclic adenosine monophosphate-regulated neuronal phosphoprotein (DARPP-32) is a critical mediator of neuroplasticity in striatal medium spiny neurons (MSNs). The work presented in this thesis used a global gene knockout (KO) construct to investigate the role of DARPP-32 in reward-based learning and performance.
Global deletion of the DARPP-32 gene disturbed performance during the intertemporal (delay) discounting procedure. DARPP-32 KO mice were less sensitive than their wildtype (WT) littermates during long delays to reinforcement. In comparison to WT mice, DARPP-32 KO mice also developed a risk-sensitive pattern of choices during a probability discounting task. Unlike the effects of DARPP-32 deletion on reinforcement along dimensions of time and risk, DARPP-32 knockout did not affect the degree of effort that subjects were willing to invest during food-reinforced progressive ratio testing. DARPP-32 KO mice also failed to exhibit Pavlovian-to-instrumental transfer and this impairment could not be rescued by administering methylphenidate prior to test. Finally, DARPP-32 KO mice were indistinguishable from WT mice during an amphetamine psychomotor sensitisation study.
Overall, the data in this thesis suggest DARPP-32 is involved in adaptive reward-based learning and performance.

Item Type: Thesis (Doctoral)
Schools and Departments: School of Psychology > Psychology
Subjects: B Philosophy. Psychology. Religion > BF Psychology > BF0180 Experimental psychology
B Philosophy. Psychology. Religion > BF Psychology > BF0501 Motivation
B Philosophy. Psychology. Religion > BF Psychology > BF0699 Genetic psychology
Depositing User: Library Cataloguing
Date Deposited: 07 Jun 2016 08:51
Last Modified: 07 Jun 2016 08:51
URI: http://sro.sussex.ac.uk/id/eprint/61352

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