Prodynorphin knockout mice demonstrate diminished age-associated impairment in spatial water maze performance

Xuan V. Nguyen, James Masse, Ashok Kumar, Rattanavijit Vijitruth, Cynthia Kulik, Mei Liu, Dong Young Choi, Thomas C. Foster, Ivan Usynin, Georgy Bakalkin, Guoying Bing

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Dynorphins, endogenous κ-opioid agonists widely expressed in the central nervous system, have been reported to increase following diverse pathophysiological processes, including excitotoxicity, chronic inflammation, and traumatic injury. These peptides have been implicated in cognitive impairment, especially that associated with aging. To determine whether absence of dynorphin confers any beneficial effect on spatial learning and memory, knockout mice lacking the coding exons of the gene encoding its precursor prodynorphin (Pdyn) were tested in a water maze task. Learning and memory assessment using a 3-day water maze protocol demonstrated that aged Pdyn knockout mice (13-17 months) perform comparatively better than similarly aged wild-type (WT) mice, based on acquisition and retention probe trial indices. There was no genotype effect on performance in the cued version of the swim task nor on average swim speed, suggesting the observed genotype effects are likely attributable to differences in cognitive rather than motor function. Young (3-6 months) mice performed significantly better than aged mice, but in young mice, no genotype difference was observed. To investigate the relationship between aging and brain dynorphin expression in mice, we examined dynorphin peptide levels at varying ages in hippocampus and frontal cortex of WT 129SvEv mice. Quantitative radioimmunoassay demonstrated that dynorphin A levels in frontal cortex, but not hippocampus, of 12- and 24-month mice were significantly elevated compared to 3-month mice. Although the underlying mechanisms have yet to be elucidated, the results suggest that chronic increases in endogenous dynorphin expression with age, especially in frontal cortex, may adversely affect learning and memory.

Original languageEnglish
Pages (from-to)254-262
Number of pages9
JournalBehavioural Brain Research
Issue number2
StatePublished - Jun 20 2005

Bibliographical note

Funding Information:
This work has been supported by NS 044157 and DAMD17-9919497 to G.B.; AG14979 and an Evelyn F. McKnight Brain Research Grant to T.C.F.; MH65055-01 and a Howard Hughes Medical Institute predoctoral fellowship to X.V.N.


  • Aging
  • Dynorphin
  • Knockout mice
  • Learning
  • Memory
  • Morris water maze
  • Opioid
  • Spatial

ASJC Scopus subject areas

  • Behavioral Neuroscience


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