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

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, M orris water maze performance, and changes in cerebral monoamines. In the op en field, eNOS-/- animals were less active than wild-type controls but show ed unimpaired habituation. In the plus-maze, an anxiogenic effect was obser ved. Proceeding from previous findings of deficits in hippocampal and neoco rtical long-term potentiation (LTP) in our eNOS-/- mice, we investigated wh ether 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 lo ng-term retention and reversal learning, eNOS-/- mice showed improved perfo rmance. In a cued version of the water maze task, eNOS-/- and control mice did not differ, implying that the superior performance of eNOS-/- animals o n the former tasks cannot be attributed solely to differences in sensorimot or capacities. The neurochemical evaluation of the eNOS-/- mice revealed in creases in the concentrations of the serotonin metabolite 5-HIAA in the cer ebellum, together with an accelerated serotonin turnover in the frontal cor tex. Furthermore, eNOS-/- mice had a higher dopamine turnover in the ventra l striatum. These findings are discussed in terms of possible concomitant e ffects on physiological parameters, such as a decreased reactivity of GABAe rgic neurotransmission or changes in vascular functions, and effects on beh avioral processes related to reinforcement, learning, and emotion.