Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.659861
Title: The effects of a non-competitive NMDA receptor antagonist FR115427 on LTP, spontaneous behaviour and performance in the water maze
Author: Nakada, Hirohisa
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1996
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Abstract:
The effects of N-methyl-D-aspartate (NMDA) receptor antagonists on learning behaviour have been studied extensively as they block long-term potentiation (LTP), the surrogate neural model for memory storage mechanisms. However, NMDA receptor antagonists also induce prominent changes in motor behaviour and the role of this drug in learning impairment by blocking LTP or by inducing behavioural abnormality remains ambiguous. Thus competitive NMDA receptor antagonists are less than satisfactory pharmacological tools for resolving the above question since the doses required for both effects are indistinguishable. Furthermore, the non-competitive NMDA receptor antagonists like MK-801 (dizocilpine) induce pronounced behavioural effects at lower doses than those required to block LTP and severe ataxia inhibits the ability of animals to perform learning tasks involving motor ability. These features greatly reduce its usefulness as a pharmacological tool. In an attempt to resolve this issue, the novel non-competitive NMDA receptor antagonist, FR115427 ((+)-1-methyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline hydrochloride), was used in this thesis. Although its binding affinity to the NMDA receptors is about 10 times less than that of MK-801, it induces relatively mild ataxia which allows testing over a wider dose range. The faster kinetic profile of FR115427 has the additional advantage that it highlights the clear-cut time dependence of the drug's action. In conclusion, the action of FR115427 on LTP was temporally and dose dependently differentiated from that on spontaneous behaviour and learning. It is suggested that non-competitive NMDA receptor antagonists impair spatial learning by an unknown mechanism that need not be related to their action on LTP.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.659861  DOI: Not available
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