Unaltered radial maze performance and brain acetylcholine of the endothelial nitric oxide synthase knockout mouse.

Proceeding from previous findings of a beneficial effect of endothelial nitric oxide synthase (eNOS) gene inactivation on negatively reinforced water maze performance, we asked whether this improvement in place learning capacities also holds for a positively reinforced radial maze task. Unlike its beneficial effects on the water maze task, eNOS gene inactivation did not facilitate radial maze performance. The acquisition performance over the days of place learning did not differ between eNOS knockout (eNOS-/-) and wild-type mice (eNOS+/+). eNOS-/- mice displayed a slight and eNOS+/+ mice a more severe working memory deficit in the place learning version of the radial maze compared to the genetic background C57BL/6 strain. Possible differential effects of eNOS inactivation, related to differences in reinforcement contingencies between the Morris water maze and radial maze tasks, behavioral strategy requirements, or to different emotional and physiological concomitants inherent in the two tasks are discussed. These task-unique characteristics might be differentially affected by the reported anxiogenic and hypertensional effects of eNOS gene inactivation. Post-mortem determination of acetylcholine concentrations in diverse brain structures revealed that acetylcholine and choline contents were not different between eNOS-/- and eNOS+/+ mice, but were increased in eNOS+/+ mice compared to C57BL/6 mice in the frontal cortex. Our findings demonstrate that phenotyping of learning and memory capacities should not rely on one learning task only, but should include tasks employing both negative and positive reinforcement contingencies in order to allow valid statements regarding differences in learning capacities between rodent strains.