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The effects of an N-methyl-D-aspartate antagonist on behaviour. Learning and memory in the rat

Butelman, Eduardo Roque; (1990) The effects of an N-methyl-D-aspartate antagonist on behaviour. Learning and memory in the rat. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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The aim of this project was to investigate the effects of N-methyl-d-aspartate (NMDA) antagonists on learning, memory and behaviour in the rat. These drugs are of particular interest due to their ability to block the triggering of ''Long Term Potentiation" (LTP, a physiological model of memory), as well as their similiarity (in behavioural and pharmacological terms) with the drug of abuse Phencyclidine (PCP); furthermore, their use In clinical trials as antineurodegeneratives may be Imminent. Dose-response studies were carried out with the compound MK-801 (Merck, Sharpe and Dohme), a potent and selective non-competitive NMDA-antagonist in the rat, with the use of photocell activity cages and 3-arm maze. Intraperitoneal doses of the compound without overt motor or stereotypical effects (0.1-0.2 mg/Kg) were then examined in various spatial tasks. An open field study confirmed that Ss under the effect of the above doses of MK-801, did not have increased levels of activity, but that habituation to a novel environment could be diminished. Deficits in efficiency were observed in the radial arm maze, and during acquisition, but not performance of a spatial ''reference memory" task. Subjects were also tested with MK-801 and PCP (3-4 mg/Kg) in the radial arm maze task with a delay interposed at the midpoint choice (drug: administration occurring either before the trial or during the interposed delay. The results from this paradigm supported the hypothesis that NMDA antagonists cause temporary deficits in a delayed stage of the encoding process, or on the retrieval of short-term memories. The results from the project overall are consistent with an involvement of NMDA-mediated neural pathways (and possibly LTP) with learning and memory. However the possible relevance of non-specific effects state-dependent learning, for example) could not be completely discounted and should be addressed by future control studies.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The effects of an N-methyl-D-aspartate antagonist on behaviour. Learning and memory in the rat
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Psychology; NMDA antagonists
URI: https://discovery.ucl.ac.uk/id/eprint/10122713
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