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 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.