Inhibition of neuronal nitric oxide reduces anxiety-like responses to pair housing

Abstract

Many psychological disorders are characterized by anxiety and alterations in social interactions. Recent studies demonstrate that the chemical messenger nitric oxide (NO) can regulate both anxiety and social behaviours. We tested whether an enzyme that produces NO in the brain, neuronal nitric oxide synthase (nNOS), serves as an interface between social interactions and anxiety-like behaviour. Several investigators have observed that mice increase anxiety-like responses in the elevated plusmaze after pair housing. nNOS gene deletion and 3-Bromo-7-Nitroindazole were used to inhibit the production of neuronal NO. Similar to previous studies, pair housing reduced open arm exploration in the elevated plus-maze. Pair housing also increased corticotropin-releasing hormone (CRH) immunoreactive cells in the paraventricular nucleus (PVN) of the hypothalamus. Inhibition of NO production increased open arm exploration in pair-housed mice but decreased open arm exploration in individually-housed mice. These results suggest that the effect of nNOS inhibition on anxiety-like responses is context dependent and that behavioural responses to social housing are altered after nNOS inhibition. This research suggests that NO may play an important role in mediating the effect social interactions have on anxiety.

Neuronal Nitric Oxide Synthase Alteration Accounts for the Role of 5-HT1AReceptor in Modulating Anxiety-Related Behaviors

“…Our previous study showed that nNOS is essential for chronic stressinduced depression in mice . Very recently, several studies have indicated that NOS is involved in anxietyrelated behaviors (Miguel and Nunes-deSouza, 2008;Workman et al, 2008). In the present study, nNOS KO mice exhibited a markedly decreased latency to feed in NSF test, suggesting an anxiolytic-like phenotype.…”

“…Our previous study showed that nNOS-derived NO contributes to chronic stress-induced depression . Recently, several studies suggest that nNOS may be related to anxiety-related behaviors (Miguel and Nunes-de-Souza, 2008;Workman et al, 2008). More importantly, nNOS plays a role in normal brain 5-HT function, especially in the 5-HT 1A and/or 5-HT 1B postsynaptic receptor function, and has significant implications for the psychiatric disorders characterized by aggressiveness and impulsivity (Chiavegatto et al, 2001).…”

Neuronal Nitric Oxide Synthase

“…Inhibition of nNOS diminishes anxiety-like responses to pair housing [57]. Also, anxiety-like behaviours in aged mice are recovered by modifying nNOS expression levels in the hippocampus or cerebellum [58].…”

DETA/NONOate, a nitric oxide donor, produces antidepressant effects by promoting hippocampal neurogenesis

“…NO has multiple functions in nervous systems and has been implicated in the regulation of various behavioral, cognitive, and emotional processes (Gulyaeva and Stepanichev 1997;Lechman and Herman 2002;Wass et al 2008;Workman et al 2008). Recent findings have shown that the NOS inhibitors L-NNA, L-NAME, and 7-nitroindazole exhibit antidepressant-like properties in the FST, which are blocked by pretreatment with L-Arg (Jefferys and Funder 1996;Harkin et al 1999;Yildiz et al 2000;Joca and Guimaraes 2006).…”