ALTERATION OF CENTRAL SEROTONIN MODIFIES ONSET AND SEVERITY OF ADJUVANT-INDUCED ARTHRITIS IN THE RAT

Objective. Previous studies have determined that depletion of serotoni n reduces the severity of hind-paw inflammation in adjuvant-induced ar thritis (AA) in the rat. We wished to (i) test the hypothesis that thi s effect may be mediated, at least in part, through a central mechanis m and (ii) to investigate further the pro-inflammatory role of seroton in we determined whether increasing serotonin using a selective seroto nin reuptake inhibitor (SSRI), to increase serotonin availability at t he active site of release, would increase inflammation. Methods. (i) S erotonin was depleted in the brain of rats with the selective neurotox in 5'7'-dihydroxytryptamine. (ii) Rats were treated with an SSRI on da ys 10, 11 and 12 following adjuvant injection. Hind-paw inflammation w as determined with plethysmometry as an index of severity of inflammat ion, and brain, pituitaries and blood were collected for assessment of changes in the hypothalamo-pituitary-adrenal (HPA) axis. Results. (i) Serotonin depletion significantly reduced hind-paw inflammation. (ii) SSRI-treated animals developed hind-paw inflammation sooner, and the severity was increased compared to vehicle-treated AA rats. The change s in the HPA axis associated with inflammation were partly reversed by this treatment. Conclusion. These data suggest a pro-inflammatory rol e for central serotonin in this disc:ase model and indicate that treat ment with SSRIs may exacerbate the development of inflammation.