L-Arginine prevents the hypothalamic serotonin release but not the hypophagia induced by interleukin 1β in normal Zucker rats

Abstract

The present study addressed the question of whether VMH serotonergic activity is affected by intracerebroventricular injection of IL-1β in normal rats and whether central nitric oxide activity participates in this process. 5-HT levels were determined in 20-min VMH microdialysates obtained from lean Zucker rats (Fa/?) receiving a single intracerebroventricular injection of 10 ng IL-1β, with or without pre-injection of 20 μg of the NO precursor l-arginine. IL-1β significantly stimulated extracellular 5-HT levels in the VMH, with a peak variation of 130 ± 37% above baseline. IL-1β also significantly reduced 4-h food intake by 23% and 24-h food intake by 58%. Treatment with l-arginine caused a significant 36% increase of 4-h intake. In animals pretreated with l-arginine, IL-1β anorexia was still present, while the VMH serotonergic stimulation was completely blocked. The present data on normal Zucker rats showed that one action of centrally administered IL-1β is the activation of the serotonergic system in the VMH. Although this activation is likely to contribute to IL-1β anorexia, it is not essential for the expression of this effect since its abolition, as induced by an NO precursor, was unable to block IL-1β anorexia. In this respect, normal Zucker rats differed from obese animals, in which hypophagia has been shown to depend on VMH serotonergic activation. It is proposed that, unlike obese rats, normal animals are able to recruit other mechanisms able to compensate for the absence of the serotonergic hypophagic effect.