DOES PHENYLETHYLAMINE HAVE A ROLE IN SCHIZOPHRENIA - LSD AND PCP UP-REGULATE AROMATIC L-AMINO-ACID DECARBOXYLASE MESSENGER-RNA LEVELS

Aromatic L-amino acid decarboxylase (AADC) is rate limiting in the pro duction of 2-phenylethylamine (2PE). AADC activity and 2PE serum conce ntrations have been found to be increased in schizophrenic patients. B oth antipsychotic and psychotogenic drugs, including amphetamine, affe ct the activity and encoding mRNA levels of AADC. Amphetamine is an an alogue of 2PE and has a similar physiological effect. We have looked a t the effects of chronic (32 day) treatment of rats with LSD (0.12 mu g/kg/day) and phencyclidine (PCP; 10 mg/kg/day) on AADC mRNA levels. B oth drugs up-regulated AADC mRNA levels in striatum, nucleus accumbens , hippocampus and cerebellum by between 50% and 150%. A splicing varia nt of AADC, present in human brain, which lacks the 3rd exon does not appear to be present in rat brain. These results are consistent with t he hypothesis that over activity of AADC leading to increased producti on of 2PE is involved in endogenous psychosis such as schizophrenia. ( C) 1997 Elsevier Science B.V.