Methylenedioxymethamphetamine-induced suppression of interleukin-1beta and tumour necrosis factor-alpha is not mediated by serotonin.
The purpose of the present study was to examine the role of serotonin release in methylenedioxymethamphetamine (MDMA)-induced immunosuppression in rats. We examined the effect of pretreatment with the selective serotonin reuptake inhibitor paroxetine, and the tryptophan hydroxylase inhibitor para-chlorophenylalanine on MDMA-induced suppression of interleukin-1beta and tumour necrosis factor (TNF)-alpha secretion following an in vivo lipopolysaccharide challenge. Although paroxetine blocked MDMA-induced serotonin depletion in the cortex and hypothalamus, it failed to alter the suppressive effect of MDMA on lipopolysaccharide-induced TNF-alpha secretion. Similarly, although para-chlorophenylalanine caused a 90% depletion in cortical and hypothalamic serotonin content, it failed to alter the suppressive effect of MDMA on lipopolysaccharide-induced interleukin-1beta or TNF-alpha secretion. In conclusion, although MDMA is a potent releaser of serotonin, the suppressive effects of MDMA on lipopolysaccharide-induced proinflammatory cytokine secretion cannot be attributed to its serotonin-releasing properties.
Connor
T J
TJ
Department of Pharmacology, National University of Ireland, Galway, Ireland. thomas.connor@nuigalway.ie
Dennedy
M C
MC
Harkin
A
A
Kelly
J P
JP
D000818:Animals; D010134:Fenclonine / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007165:Immunosuppression Therapy; D007375:Interleukin-1 / Q000097:blood / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000276:immunology / Q000494:pharmacology*; D017374:Paroxetine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D010134:Fenclonine; D007375:Interleukin-1; D008070:Lipopolysaccharides; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D017374:Paroxetine; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D014409:Tumor Necrosis Factor-alpha