The inhibition of tryptophan hydroxylase, not protein synthesis, reduces the brain trapping of α-methyl-L-tryptophan:: an autoradiographic study

The effects of the tryptophan hydroxylase (TPH) inhibitor p-chlorophenylalanine (PCPA; 200 mg/kg; 3 days), and of the protein synthesis inhibitor cycloheximide (CXM, 2 mg/kg), on regional serotonin (5-HT) synthesis were studied using the alpha-[C-14]methyl-L-tryptophan (alpha-[C-14]MTrp) autoradiographic method. The objectives of these investigations were to evaluate the changes, if any, on 5-HT synthesis, as measured with alpha-MTrp method, following the inhibition of TPH by PCPA, or the inhibition of proteins synthesis by CXM. The rats were used in the tracer experiment approximately 24 h after the last dose of PCPA was administered, and in the CXM experiments, they were used 30 min following a single injection of CXM. In both experiments, the control rats were injected with the same volume of saline (0.5 ml/kg; s.c.) and at the same times as the drug injections. The results demonstrate that trapping of alpha-MTrp, which is taken to be related to brain 5-HT synthesis, is drastically reduced (40-80%) following PCPA treatment. The inhibition of protein synthesis with CXM did not have a significant effect on the global brain trapping of alpha-MTrp and 5-HT synthesis. These findings suggest that the brain trapping of alpha-[C-14]MTrp relates to brain 5-HT synthesis, but not to brain protein synthesis. (C) 2002 Elsevier Science Ltd. All rights reserved.