title: Contribution of N-methyl-D-aspartate receptors to attention and episodic spatial memory during senescence.
abstract: A decrease in N-methyl-D-aspartate receptor (NMDAR) function is associated with age-related cognitive impairments. However, NMDAR antagonists are prescribed for cognitive decline associated with age-related neurodegenerative disease, raising questions as to the role of NMDAR activity in cognitive function during aging. The current studies examined effects of NMDAR blockade on cognitive task that are sensitive to aging. Young and middle-age rats were trained on the five-choice serial reaction time task (5-CSRTT) and challenged with MK-801 (0.025, 0.05, and 0.1mg/kg or vehicle). Attention deficits were apparent in middle-age and performance of young and middle-age rats was enhanced for low doses of MK-801 (0.025 and 0.05). The beneficial effects on attention were reversed by the highest dose of MK-801. Older animals exhibited a delay-dependent impairment of episodic spatial memory examined on a delayed-matching to place water maze task. Similarly, a low dose of MK-801 (0.05mg/kg) impaired performance with increasing delay and aged animals were more susceptible to disruption by NMDAR blockade. Despite MK-801 impairment of episodic spatial memory, MK-801 had minimal effects on spatial reference memory. Our results confirm that NMDARs contribute to rapidly acquired and flexible spatial memory and support the idea that a decline in NMDAR function contributes to the age-related impairments in cognition.
authors.affiliation: Noldus Information Technology, 1503 Edwards Ferry Road, Suite 310, Leesburg, VA 20176, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Guidi
authors.affiliation: Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Asha
authors.initials: A
authors.lastname: Rani
authors.affiliation: Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Semir
authors.initials: S
authors.lastname: Karic
authors.affiliation: Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Barrett
authors.initials: B
authors.lastname: Severance
authors.affiliation: Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA. Electronic address: Kash@ufl.edu.
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA. Electronic address: Foster1@ufl.edu.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Foster
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D061212:Memory, Episodic; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D065852:Spatial Memory / Q000187:drug effects* / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate
keywords: Aging; Attention; Episodic memory; Hippocampus; MK-801; NMDA receptor; Prefrontal cortex