5-HT1C/5-HT2 receptor blockade prevents 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane-, but not stress-induced increases in brain tryptophan.
We have previously shown that acute administration of the 5-HT1C/5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane (DOI), elevates brain tryptophan levels. The present work aimed to investigate the mechanisms responsible for this elevation. Acute s.c. administration of a 2-mg/kg dose of DOI increased brain tryptophan levels but did not affect either plasma free tryptophan, plasma total tryptophan, brain 5-HT, or brain 5-hydroxyindoleacetic acid. Pretreatment with the 5-HT1C/5-HT2 receptor antagonist, LY 53857, prevented the DOI-induced increase in brain tryptophan levels, whilst the increase was reduced by the 5-HT2 receptor/alpha 1-adrenoceptor antagonist, ketanserin, and to a lesser extent, by the ganglionic blocker, chlorisondamine. On the other hand, pretreatment with either the peripherally acting 5-HT1C/5-HT2 receptor blocker, BW 501C67, the 5-HT uptake enhancer, tianeptine, the 5-HT uptake blocker, paroxetine, or the beta 2-adrenoceptor antagonist, ICI 118.551, proved ineffective. Lastly, pretreatment with LY 53857 did not affect the immobilization-induced elevation in brain tryptophan levels. It is concluded that the elevation in brain tryptophan levels induced by DOI but not that induced by stress is due to central 5-HT1C and 5-HT2 receptor stimulation.
Chaouloff
F
F
Laboratoire de Pharmacologie, CNRS, CHU Necker, Paris, France.
Layeillon
C
C
Baudrie
V
V
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000662:Amphetamines / Q000037:antagonists & inhibitors*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004873:Ergolines / Q000494:pharmacology; D005730:Ganglionic Blockers / Q000494:pharmacology; D007211:Indoles / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists / Q000037:antagonists & inhibitors*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013312:Stress, Physiological / Q000378:metabolism*; D014364:Tryptophan / Q000097:blood / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D000662:Amphetamines; D004873:Ergolines; D005730:Ganglionic Blockers; D007211:Indoles; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D014364:Tryptophan; C032663:LY 53857; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine