Effects of 5-hydroxytryptophan on extracellular serotonin in the spinal cord of rats with experimental allergic encephalomyelitis.
Serotonin (5-HT) and the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA) were collected by in vivo dialysis in the lumbar spinal cord of control rats and rats with hindlimb paralysis induced by experimental allergic encephalomyelitis (EAE). Both 5-HT and 5-HIAA were significantly decreased in baseline samples from EAE rats compared to controls. This decrease in extracellular 5-HT and 5-HIAA in the EAE rats was accompanied by marked morphological changes in spinal cord axons and axon terminal plexuses that were stained for 5-HT-like immunoreactivity. The 5-HT precursor, 5-hydroxytryptophan (5-HTP)-increased 5-HT and 5-HIAA levels in dialysate samples from both control and EAE animals. However, the 5-HTP-induced increase in extracellular 5-HT was significantly greater in the EAE rats than in the controls, despite a lower baseline 5-HT level in the EAE animals. In contrast to 5-HT, both baseline and post-5-HTP levels of 5-HIAA were significantly higher in control animals than in EAE animals. The decreased extracellular 5-HT and 5-HIAA in baseline samples from the EAE rats compared to controls is probably a consequence of the damage to descending 5-HT axons and axon terminals that occurs during the disease. The larger increase in extracellular 5-HT in EAE animals after precursor injection may reflect both decreased 5-HT reuptake from the extracellular space by damaged 5-HT terminals and disruption of the blood-brain barrier that allows entry into the central nervous system of 5-HT that was synthesized from 5-HTP in the periphery.
Samathanam
G K
GK
Department of Veterinary and Comparative Anatomy, Washington State University, Pullman 99164.
White
S R
SR
Kalivas
P W
PW
Duffy
P
P
D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000818:Animals; D048588:Benzoxazines; D003956:Dialysis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D010078:Oxazines; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
D048588:Benzoxazines; D010078:Oxazines; C028911:cresyl violet; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D006916:5-Hydroxytryptophan