Authors: Sophie Dix Gary Gilmour Slavinka Potts Janice W Smith Mark Tricklebank
Publish Date: 2010/07/31
Volume: 212, Issue: 2, Pages: 227-242
Abstract
The range of cognitive and psychotomimetic effects produced by antagonists of the NmethylDaspartate NMDA receptor has lead to widespread usage of these molecules as pharmacological models of cognitive impairment for drug discovery Historically NMDA receptor antagonists have been used interchangeably on the assumption that they produce analogous effectsNaïve male Lister Hooded rats were subjected to a series of tests in which they were required to learn a simple visuoauditory conditional discrimination They then underwent testing in a delayed discrimination test followed by rule reversal and rule extinction testsAll NMDA receptor antagonists tested impaired acquisition performance and with the exception of ketamine and the GluN2A preferring antagonist NVPAAM077 impaired consolidation of extinction GluN2B antagonism produced a singular profile with potentially enhanced delayed discrimination performance and reduced hit rates in the reversal phase Only PCP phencyclidine and ketamine disrupted performance in the delay phase but did so in a delayindependent manner MK801 PCP and memantine all increased the hit rate in the reversal phase whilst only MK801 and PCP impaired extinction per seNMDA receptordependent mechanisms are requisite in the acquisition of a simple conditional discrimination and consolidation of extinction Their role in working memory and reversal tasks appear to be less critical and potentially specific to the paradigm and NMDA receptor antagonist used It is clearly misleading to generalise across NMDA antagonists with respect to their preclinical cognitive profile
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