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MK-801 improves retention in aged rats: implications for altered neural plasticity in age-related memory deficits.
Neurobiol Learn Mem. 1999 Mar; 71(2):194-206.NL

Abstract

Alterations in N-methyl-d-aspartate receptor (NMDAR)-dependent synaptic plasticity, characteristic of aged rodents, may contribute to impaired memory with advanced age. The purpose of the current research was to examine whether NMDARs contribute to rapid forgetting on a spatial memory task. Aged (22-24 months) and adult (3-6 months) male Fischer 344 rats received 18 training trials, over a period of 3 to 4 h, on the spatial version of the Morris water maze. Immediately after training, a standard free-swim probe trial was administered to assess the acquisition of spatial bias, which was determined by the percent of time spent in the goal quadrant and the number of platform crossings. Rats then received injections of the noncompetitive NMDAR antagonist, (+)-10, 11-dihydro-5methyl-5H-dibenzo(a,b)cycloheptene-5,10 imine (MK-801, 0. 05 mg/kg, i.p.), or a vehicle injection of equal volume. Approximately 24 h later, rats were administered a second free-swim probe trial to assess retention of spatial bias. All age/drug groups exhibited a spatial bias on the acquisition probe, with adults generally outperforming the aged rats. On the retention probe, this spatial bias continued to be shown by adult rats, regardless of treatment. For the aged group, in contrast, only MK-801-injected rats maintained a spatial bias on the retention probe, suggesting that NMDAR activity may be involved in rapid forgetting during aging. Because blockade of NMDARs also may impair new learning, which may, in turn, protect previously stored information from retroactive interference, rats in a second experiment received post-training injections of scopolamine (0.05 mg/kg), a compound known to inhibit learning. However, scopolamine did not enhance retention in the aged group, consistent with the hypothesis that MK-801 influenced memory in aged rats through its actions on NMDAR-dependent synaptic plasticity.

Authors+Show Affiliations

College of Medicine, University of Kentucky, Lexington, Kentucky 40536, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10082639

Citation

Norris, C M., and T C. Foster. "MK-801 Improves Retention in Aged Rats: Implications for Altered Neural Plasticity in Age-related Memory Deficits." Neurobiology of Learning and Memory, vol. 71, no. 2, 1999, pp. 194-206.
Norris CM, Foster TC. MK-801 improves retention in aged rats: implications for altered neural plasticity in age-related memory deficits. Neurobiol Learn Mem. 1999;71(2):194-206.
Norris, C. M., & Foster, T. C. (1999). MK-801 improves retention in aged rats: implications for altered neural plasticity in age-related memory deficits. Neurobiology of Learning and Memory, 71(2), 194-206.
Norris CM, Foster TC. MK-801 Improves Retention in Aged Rats: Implications for Altered Neural Plasticity in Age-related Memory Deficits. Neurobiol Learn Mem. 1999;71(2):194-206. PubMed PMID: 10082639.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MK-801 improves retention in aged rats: implications for altered neural plasticity in age-related memory deficits. AU - Norris,C M, AU - Foster,T C, PY - 1999/3/20/pubmed PY - 1999/3/20/medline PY - 1999/3/20/entrez SP - 194 EP - 206 JF - Neurobiology of learning and memory JO - Neurobiol Learn Mem VL - 71 IS - 2 N2 - Alterations in N-methyl-d-aspartate receptor (NMDAR)-dependent synaptic plasticity, characteristic of aged rodents, may contribute to impaired memory with advanced age. The purpose of the current research was to examine whether NMDARs contribute to rapid forgetting on a spatial memory task. Aged (22-24 months) and adult (3-6 months) male Fischer 344 rats received 18 training trials, over a period of 3 to 4 h, on the spatial version of the Morris water maze. Immediately after training, a standard free-swim probe trial was administered to assess the acquisition of spatial bias, which was determined by the percent of time spent in the goal quadrant and the number of platform crossings. Rats then received injections of the noncompetitive NMDAR antagonist, (+)-10, 11-dihydro-5methyl-5H-dibenzo(a,b)cycloheptene-5,10 imine (MK-801, 0. 05 mg/kg, i.p.), or a vehicle injection of equal volume. Approximately 24 h later, rats were administered a second free-swim probe trial to assess retention of spatial bias. All age/drug groups exhibited a spatial bias on the acquisition probe, with adults generally outperforming the aged rats. On the retention probe, this spatial bias continued to be shown by adult rats, regardless of treatment. For the aged group, in contrast, only MK-801-injected rats maintained a spatial bias on the retention probe, suggesting that NMDAR activity may be involved in rapid forgetting during aging. Because blockade of NMDARs also may impair new learning, which may, in turn, protect previously stored information from retroactive interference, rats in a second experiment received post-training injections of scopolamine (0.05 mg/kg), a compound known to inhibit learning. However, scopolamine did not enhance retention in the aged group, consistent with the hypothesis that MK-801 influenced memory in aged rats through its actions on NMDAR-dependent synaptic plasticity. SN - 1074-7427 UR - https://www.unboundmedicine.com/medline/citation/10082639/MK_801_improves_retention_in_aged_rats:_implications_for_altered_neural_plasticity_in_age_related_memory_deficits_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1074-7427(98)93864-3 DB - PRIME DP - Unbound Medicine ER -