title: Comparison of various N-methyl-D-aspartate receptor antagonists in a model of short-term memory and on overt behaviour.
abstract: This study examined the effects on rat behaviour of antagonists acting at various sites on the N-methyl-D-aspartate (NMDA) receptor complex, i.e. the glutamate recognition site (CPP), ion channel (dizocilpine), glycine recognition site [(+)-HA-966] and the NR2B subunit-selective compound ifenprodil. Specifically, the effects of these agents were examined on working memory, assessed using the operant delayed match-to-position task (DMTP), and overt behaviour, assessed (a) in animals responding for food under a variable interval 20-s (VI20) schedule and (b) by spontaneous behaviour. Dizocilpine, CPP and (+)-HA-966 each reduced accuracy in the DMTP task independent of delay. At equivalent doses, changes in locomotor behaviour and VI20 responding were evident. In contrast, ifenprodil failed to impair accuracy in the DMTP task, even at doses that affected other performance measures and reduced VI20 responding. The relevance of these observations to neuroprotective and anticonvulsant doses of these compounds is considered.
authors.affiliation: Department of Biosciences, University of Hertfordshire, Hatfield, Herts, UK. k.m.doyle@herts.ac.uk
authors.forename: K M
authors.initials: KM
authors.lastname: Doyle
authors.forename: S
authors.initials: S
authors.lastname: Feerick
authors.forename: D L
authors.initials: DL
authors.lastname: Kirkby
authors.forename: A
authors.initials: A
authors.lastname: Eddleston
authors.forename: G A
authors.initials: GA
authors.lastname: Higgins
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D012055:Reinforcement Schedule
chemical_list: D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D010880:Piperidines; D011760:Pyrrolidinones; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C001369:1-hydroxy-3-amino-2-pyrrolidone; C010739:ifenprodil