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Pharmacol Biochem Behav. 2009 Jan;91(3):453-60. doi: 10.1016/j.pbb.2008.08.028. Epub 2008 Sep 8.

Fear memory impairing effects of systemic treatment with the NMDA NR2B subunit antagonist, Ro 25-6981, in mice: attenuation with ageing.

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1
Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse, NIH, Rockville, MD 20852-9411, USA.

Abstract

N-methyl-D-aspartate receptors (NMDARs) are mediators of synaptic plasticity and learning and are implicated in the pathophysiology of neuropsychiatric disease and age-related cognitive dysfunction. NMDARs are heteromers, but the relative contribution of specific subunits to NMDAR-mediated learning is not fully understood. We characterized pre-conditioning systemic treatment of the NR2B subunit-selective antagonist Ro 25-6981 for effects on multi-trial, one-trial and low-shock Pavlovian fear conditioning in C57BL/6J mice. Ro 25-6981 was also profiled for effects on novel open field exploration, elevated plus-maze anxiety-like behavior, startle reactivity, prepulse inhibition of startle, and nociception. Three-month (adult) and 12-month old C57BL/6Tac mice were compared for Ro 25-6981 effects on multi-trial fear conditioning, and corticolimbic NR2B protein levels. Ro 25-6981 moderately impaired fear learning in the multi-trial and one-trial (but not low-shock) conditioning paradigms, but did not affect exploratory or anxiety-related behaviors or sensory functions. Memory impairing effects of Ro 25-6981 were absent in 12-month old mice, although NR2B protein levels were not significantly altered. Present data provide further evidence of the memory impairing effects of selective blockade of NR2B-containing NMDARs, and show loss of these effects with ageing. This work could ultimately have implications for elucidating the pathophysiology of learning dysfunction in neuropsychiatric disorders and ageing.

PMID:
18809426
PMCID:
PMC2645594
DOI:
10.1016/j.pbb.2008.08.028
[Indexed for MEDLINE]
Free PMC Article
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