Methylenedioxymethamphetamine-induced suppression of interleukin-1 beta and tumour necrosis factor-alpha is not mediated by serotonin

The purpose of the present study was to examine the role of serotonin relea se in methylenedioxymethamphetamine (MDMA)-induced immunosuppression in rat s. We examined the effect of pretreatment with the selective serotonin reup take inhibitor paroxetine, and the tryptophan hydroxylase inhibitor para-ch lorophenylalanine on MDMA-induced suppression of interleukin-1 beta and tum our necrosis factor (TNF)-alpha secretion following an in vivo lipopolysacc haride challenge. Although paroxetine blocked MDMA-induced serotonin deplet ion in the cortex and hypothalamus, it failed to alter the suppressive effe ct of MDMA on lipopolysaccharide-induced TNF-alpha secretion. Similarly, al though para-chlorophenylalanine caused a 90% depletion in cortical and hypo thalamic serotonin content, it failed to alter the suppressive effect of MD MA on lipopolysaccharide-induced interleukin-1 beta or TNF-alpha secretion. In conclusion, although MDMA is a potent releaser of serotonin, the suppre ssive effects of MDMA on lipopolysaccharide-induced proinflammatory cytokin e secretion cannot be attributed to its serotonin-releasing properties. (C) 2001 Elsevier Science B.V. All rights reserved.