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d ‐amino acid oxidase knockout ( Dao −/− ) mice show enhanced short‐term memory performance and heightened anxiety, but no sleep or circadian rhythm disruption
Author(s) -
Pritchett David,
Hasan Sibah,
Tam Shu K. E.,
Engle Sandra J.,
Brandon Nicholas J.,
Sharp Trevor,
Foster Russell G.,
Harrison Paul J.,
Bannerman David M.,
Peirson Stuart N.
Publication year - 2015
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12880
Subject(s) - circadian rhythm , spontaneous alternation , endocrinology , elevated plus maze , knockout mouse , psychology , medicine , neuroscience , endogeny , agonist , receptor , anxiety , biology , hippocampus , psychiatry
d ‐amino acid oxidase ( DAO , DAAO ) is an enzyme that degrades d ‐serine, the primary endogenous co‐agonist of the synaptic N ‐methyl‐ d ‐aspartate receptor. Convergent evidence implicates DAO in the pathophysiology and potential treatment of schizophrenia. To better understand the functional role of DAO , we characterized the behaviour of the first genetically engineered Dao knockout ( Dao −/− ) mouse. Our primary objective was to assess both spatial and non‐spatial short‐term memory performance. Relative to wildtype ( Dao +/+ ) littermate controls, Dao −/− mice demonstrated enhanced spatial recognition memory performance, improved odour recognition memory performance, and enhanced spontaneous alternation in the T‐maze. In addition, Dao −/− mice displayed increased anxiety‐like behaviour in five tests of approach/avoidance conflict: the open field test, elevated plus maze, successive alleys, light/dark box and novelty‐suppressed feeding. Despite evidence of a reciprocal relationship between anxiety and sleep and circadian function in rodents, we found no evidence of sleep or circadian rhythm disruption in Dao −/− mice. Overall, our observations are consistent with, and extend, findings in the natural mutant ddY/ Dao − line. These data add to a growing body of preclinical evidence linking the inhibition, inactivation or deletion of DAO with enhanced cognitive performance. Our results have implications for the development of DAO inhibitors as therapeutic agents.