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  • Title: 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.
    Author: Frisch C, Dere E, Silva MA, Godecke A, Schrader J, Huston JP.
    Journal: J Neurosci; 2000 Sep 01; 20(17):6694-700. PubMed ID: 10964974.
    Abstract:
    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.
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