The role of endogenous serotonin in adjuvant-induced arthritis in the rat.

We have investigated the effects of serotonin depletion on the progress and severity of adjuvant-induced arthritis in the Piebald-Viral-Glaxo (PVG) strain of rat. Total body depletion of serotonin was achieved using p-chlorophenylalanine given i.p. Two paradigms were investigated. First we depleted serotonin at the time of injection of the adjuvant to determine whether serotonin was involved in the initial induction phase. Secondly, we depleted serotonin at the time of onset of the inflammation. Serotonin levels in the hypothalamic paraventricular nucleus (PVN) were reduced by > 95%. Depletion at the time of induction had no effect on the severity of the disease (determined by the increase (determined by the increase in hind paw volume) 14 days after injection of the adjuvant. In contrast, depletion at the time of onset of the disease resulted in a significant reduction in severity at day 14, suggesting a pro-inflammatory role for serotonin in this model. The decrease in corticotrophin-releasing factor (CRF) mRNA in the PVN associated with the development of adjuvant arthritis in PVG rat was reversed in the serotonin-depleted animals. Central serotonin could be one of the factors responsible for the reduced expression of CRF mRNA in response to adjuvant-induced arthritis in this rat strain. These data suggest that serotonin antagonists may be efficacious in reducing the severity of acute inflammatory episodes.