Tryptophan pretreatment augmentation of p-chloroamphetamine-induced serotonin and dopamine release and reduction of long-term neurotoxicity.
The impact of tryptophan (TRP) pretreatment on the neurochemical effects of p-chloroamphetamine (PCA) was investigated. The neurotoxic effects of PCA on serotonin (5-HT) neurons, the acute effects of PCA on extracellular 5-HT and dopamine (DA), and the displacement by PCA of whole blood 5-HT were examined. TRP pretreatment (400 mg/kg of the methyl ester) significantly reduced the long-term (1 week) decrease in tissue 5-HT resulting from PCA (2 mg/kg, i.p., of the hydrochloride salt) in the prefrontal cortex and striatum, but not in the dorsal hippocampus. Microdialysis studies in awake animals showed that this pretreatment regimen resulted in augmented PCA-induced increases in extracellular 5-HT (4-fold) and DA (2-fold). TRP pretreatment also resulted in increased displacement of 5-HT from whole blood. The implications of these results toward possible mechanisms of action of PCA-induced neurotoxicity are discussed.
Iyer
R N
RN
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520.
Sprouse
J S
JS
Aghajanian
G K
GK
Roth
R H
RH
Bradberry
C W
CW
D000818:Animals; D001923:Brain Chemistry; D004298:Dopamine / Q000378:metabolism*; D004357:Drug Synergism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000097:blood / Q000378:metabolism*; D014364:Tryptophan / Q000494:pharmacology*; D010133:p-Chloroamphetamine / Q000494:pharmacology* / Q000633:toxicity
D012701:Serotonin; D010133:p-Chloroamphetamine; D014364:Tryptophan; D004298:Dopamine