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• W2063315308 abstract "Administration of bacterial lipopolysaccharide (LPS) to rodents induces hypophagia, body weight loss and hypolocomotion, a constellation of symptoms collectively referred to as ‘sickness behaviour’. We examined the role of the gaseous transmitter nitric oxide (NO) in mediating LPS-induced sickness behaviour in rats. Treatment with the non-selective NO synthase (NOS) inhibitor N^G-nitro-<i>L</i>-arginine (<i>L</i>-NA) (20 mg/kg; i.p.) increased the severity of LPS-induced sickness behaviour in rats, suggesting that endogenous NO does not act as a mediator of LPS-induced sickness behaviour, but may rather have a protective role, acting in an inhibitory feedback manner to limit LPS-induced sickness. To evaluate the role of the different NOS isoforms in this response, we examined the effect of the neuronal NOS inhibitor, 7-nitroindazole (7-NI; 25 and 50 mg/kg; i.p.), and the inducible NOS inhibitor, aminoguanidine (AGN; 50 and 100 mg/kg; i.p.). Neither 7-NI nor AGN significantly altered LPS-induced sickness behaviour. Therefore, it is likely that the endothelial isoform of NOS mediates the effect of <i>L</i>-NA on LPS-induced sickness behaviour. As pro-inflammatory cytokines are mediators of LPS-induced sickness behaviour, we examined the effect of <i>L</i>-NA (20 mg/kg; i.p.) on LPS-induced interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α production. <i>L</i>-NA increased LPS-induced TNF-α without significantly altering IL-1β or IL-6 production. Moreover, pre-treatment with the TNF-α inhibitor pentoxyfilline (25 mg/kg; i.p.) largely reversed the augmenting effect of <i>L</i>-NA on LPS-induced sickness behaviour, suggesting that the ability of <i>L</i>-NA to increase TNF-α production underpinned its ability to increase the severity of sickness. In conclusion, <i>L</i>-NA increases the severity of LPS-induced sickness behaviour, most likely by blocking the tonic inhibitory action of constitutively produced NO on TNF-α production." @default.
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• W2063315308 date "2002-01-01" @default.
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• W2063315308 title "Inhibition of Constitutive Nitric Oxide Production Increases the Severity of Lipopolysaccharide-Induced Sickness Behaviour: A Role for TNF-α" @default.
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• W2063315308 doi "https://doi.org/10.1159/000071478" @default.
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