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Title: Nicotine induced improvements in cognition : a possible role for the α7 nicotinic acetylcholine receptor
Author: Young, Jared W.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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Assessment of sustained attention in rodents can be performed using the 5-choice serial reaction-time (5-CSR) task; analogous to the continuous performance test used in man. A 5-CSR protocol was established which allowed the demonstration of nicotine-induced improvements in sustained attention in mice. In this task α7 nAChR knockout (KO) mice exhibited impaired acquisition and performance, providing additional evidence that this receptor may be a valid therapeutic target for cognitive enhancement. In order to investigate the role of nAChR manipulation on working memory, the odour span task, a test of olfactory working memory capacity, was established in mice. Nicotine administration did not improve performance of C57B1/6J mice probably as a consequence of ceiling effects. Transgenic mice over-expressing human caspase-3 (hc-3) displayed a robust impairment in the task that was attenuated by nicotine administration. Moreover α7 nAChR KO mice exhibited impaired acquisition and performance in the task but in a different pattern to that of the hc-3 mice. This pattern may reflect an impaired ability to attend to the task as opposed to a working memory deficit alone. These demonstrations provide further support for a role of the α7 nAChR in cognition. Tg2576 mice represent the best well characterised transgenic model of AD, however there remains a dearth of information on their attentional and olfactory capabilities. The mice exhibited a deficit in sustained attention in the 5-CSR task, as well as an age-related impairment in the odour span task. In conclusion the development of the 5-CSR task for mice was used to identify a nicotine-induced improvement in normal mice and impaired performance in α7 KO and Tg2576 mice. In summary these data provide some evidence for a role of the α7 nAChR in nicotine-induced improvement in cognition, and with the tasks developed provide new tools for the assessment of putative cognitive enhancing compounds.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available