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

Abstract

Nitric oxide (NO) has been implicated in the control of emotion, learning, and memory. We have examined endothelial NO synthase-deficient mice (eNOSϪ/Ϫ) 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, eNOSϪ/Ϫ 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 eNOSϪ/Ϫ 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, eNOSϪ/Ϫ mice showed improved performance. In a cued version of the water maze task, eNOSϪ/Ϫ and control mice did not differ, implying that the superior performance of eNOSϪ/Ϫ animals on the former tasks cannot be attributed solely to differences in sensorimotor capacities. The neurochemical evaluation of the eNOSϪ/Ϫ 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, eNOSϪ/Ϫ 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.

Stimulation of P2Y1 Receptors Causes Anxiolytic-like Effects in the Rat Elevated Plus-maze: Implications for the Involvement of P2Y1 Receptor-Mediated Nitric Oxide Production

“…Anxiogenic-like effects were also reported after intra-amygdala or intra-hippocampal injection of L-NOARG (Monzon et al, 2001). On the one hand, eNOS-deficient mice showed an increase in anxietyrelated behavior in the plus-maze in comparison with the wild-type controls (Frisch et al, 2000). On the other hand, anxiolytic-like effects of L-NAME have been reported in the rat elevated plus-maze after i.p.…”

Comparing mechanisms of host manipulation across host and parasite taxa

“…However, NO also functions as a neurotransmitter (although it is not stored in synaptic vesicles and is synthesized as needed) that can influence brain monoaminergic activity. NO has been shown to influence serotonin (5-HT) and dopamine (DA) release in rodents (Dunn, 2006;Frisch et al, 2000;Helluy and Thomas, 2010), and therefore elevated NO activity likely plays a role in the decreased serotonergic activity observed in the brains of infected gammarids (Helluy and Thomas, 2003;Helluy and Thomas, 2010).…”

Hemispheric Dissociation of the Involvement of NOS Isoforms in Memory for Discriminated Avoidance in the Chick

“…In contrast, single mutant mice retain the capacity for normal LTP (O'Dell et al 1994;Son et al 1996), suggesting that either isoform is sufficient for this putative mechanism of memory formation. Interestingly, mice deficient for the eNOS gene are superior in water maze performance (Frisch et al 2000), but no different from their controls on radial maze performance (Dere et al 2001), suggesting that NOS requirements may vary across tasks. Although the majority of pharmacobehavioral studies demonstrating a role for nitric oxide in learning or memory have used general NOS inhibitors, there is some evidence that implicates specific isoforms in memory processing.…”