Rn. Iyer et al., TRYPTOPHAN PRETREATMENT AUGMENTATION OF P-CHLOROAMPHETAMINE-INDUCED SEROTONIN AND DOPAMINE RELEASE AND REDUCTION OF LONG-TERM NEUROTOXICITY, Biochemical pharmacology, 48(7), 1994, pp. 1501-1508
The impact of tryptophan (TRP) pretreatment on the neurochemical effec
ts of p-chloroammphetamine (PCA) was investigated. The neurotoxic effe
cts of PCA on serotonin (5-HT) neurons, the acute effects of PCA on ex
tracellular 5-HT and dopamine (DA), and the displacement by PCA of who
le blood 5-HT were examined. TRP pretreatment (400 mg/kg of the methyl
ester) significantly reduced the long-term (1 week) decrease in tissu
e 5-HT resulting from PCA (2 mg/kg, i.p., of the hydrochloride salt) i
n the prefrontal cortex and striatum, but not in the dorsal hippocampu
s. Microdialysis studies in awake animals showed that this pretreatmen
t regimen resulted in augmented PCA-induced increases in extracellular
5-HT (4-fold) and DA (2-fold). TRP pretreatment also resulted in incr
eased displacement of 5-HT from whole blood. The implications of these
results toward possible mechanisms of action of PCA-induced neurotoxi
city are discussed.