Previous research employing modulation of 5-HT2C receptors (5-HT2CRs) in rodents has identified a potential role in mediating cognitive flexibility. The work presented in this thesis explores the effects of systemic administration of the selective 5-HT2CR antagonist SB242084 on a range of Pavlovian and operant learning paradigms used to model cognitive flexibility and reward-based learning in mice. Based on a key design difference in previous research reporting discrepant outcomes, trial initiation requirements were manipulated. However the effect of SB242084 administration relative to vehicle-treatment was consistent with prior reports of impaired reversal performance following reductions in 5-HT2CR activity, regardless of whether trials were automatically or self-initiated. In contrast, performance on a probabilistic reversal learning task was enhanced by drug-treatment, raising the possibility that task difficulty mediates the effect of this manipulation on performance. A drug-related enhancement in the ability to overcome learned non-reward at the previously incorrect location was additionally demonstrated under probabilistic reversal conditions, with no effect on perseverance at the previously correct location. However, performance of drug-treated animals in two closely related tasks demonstrated impaired extinction learning but intact development of latent inhibition to a pre-exposed stimulus. The effect of SB242084 on incentive motivation was additionally explored, but did not impact upon the acquisition of a sign-tracking response to a conditioned stimulus, or a subsequent reversal; suggesting that 5-HT2CRs may be more critically involved in instrumental than Pavlovian learning. These experiments reveal a complex picture for the involvement of 5-HT2CRs in flexible cognition, however, systemic manipulations may not be optimal for dissecting their role. Therefore, a final study explored the expression of c-Fos immunoreactivity in response to reversal learning. A broad network was activated by elements of the reversal task, including regions of the prefrontal cortex and amygdala, providing a basis for future studies targeting components of this circuitry.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:714788 |
| Date | January 2017 |
| Creators | Borton, Maxine |
| Publisher | University of Sussex |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://sro.sussex.ac.uk/id/eprint/68088/ |
Page generated in 0.0021 seconds