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The Journal of Neuroscience, September 1, 2000, 20(17):6694-6700
Superior Water Maze Performance and Increase in Fear-Related
Behavior in the Endothelial Nitric Oxide Synthase-Deficient Mouse
Together with Monoamine Changes in Cerebellum and Ventral
Striatum
Christian
Frisch1,
Ekrem
Dere1,
Maria Angelica
De Souza
Silva1,
Axel
Gödecke2,
Jürgen
Schrader2, and
Joseph P.
Huston1
1 Institute of Physiological Psychology and
2 Institute of Physiology, Center for Biological and
Medical Research, University of Düsseldorf, D-40225
Düsseldorf, Germany
Nitric oxide (NO) has been implicated in the control of emotion,
learning, and memory. We have examined endothelial NO
synthase-deficient mice (eNOS / ) in terms of habituation to an open
field, elevated plus-maze behavior, Morris water maze performance, and
changes in cerebral monoamines. In the open field, eNOS / animals
were less active than wild-type controls but showed unimpaired
habituation. In the plus-maze, an anxiogenic effect was observed.
Proceeding from previous findings of deficits in hippocampal and
neocortical long-term potentiation (LTP) in our eNOS / mice, we
investigated whether these animals also express deficits in learning
tasks that have been linked to hippocampal function and LTP.
Unexpectedly, eNOS gene disruption led to accelerated place learning in
the water maze. Furthermore, during long-term retention and reversal learning, eNOS / mice showed improved performance. In a cued version
of the water maze task, eNOS / and control mice did not differ,
implying that the superior performance of eNOS / animals on the
former tasks cannot be attributed solely to differences in sensorimotor
capacities. The neurochemical evaluation of the eNOS / mice revealed
increases in the concentrations of the serotonin metabolite 5-HIAA in
the cerebellum, together with an accelerated serotonin turnover in the
frontal cortex. Furthermore, eNOS / mice had a higher dopamine
turnover in the ventral striatum. These findings are discussed in terms
of possible concomitant effects on physiological parameters, such as a
decreased reactivity of GABAergic neurotransmission or changes in
vascular functions, and effects on behavioral processes related to
reinforcement, learning, and emotion.
Key words:
endothelial nitric oxide synthase; mouse mutants; genetic
inactivation; anxiety; activity; learning; memory; serotonin; dopamine; cerebellum; ventral striatum
Copyright © 2000 Society for Neuroscience 0270-6474/00/20176694-07$05.00/0
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