Does phenylethylamine have a role in schizophrenia?: LSD and PCP up-regulate aromatic L-amino acid decarboxylase mRNA levels.
Aromatic L-amino acid decarboxylase (AADC) is rate limiting in the production of 2-phenylethylamine (2PE). AADC activity and 2PE serum concentrations have been found to be increased in schizophrenic patients. Both antipsychotic and psychotogenic drugs, including amphetamine, affect the activity and encoding mRNA levels of AADC. Amphetamine is an analogue of 2PE and has a similar physiological effect. We have looked at the effects of chronic (32 day) treatment of rats with LSD (0.12 microg/kg/day) and phencyclidine (PCP; 10 mg/kg/day) on AADC mRNA levels. Both drugs up-regulated AADC mRNA levels in striatum, nucleus accumbens, hippocampus and cerebellum by between 50% and 150%. A splicing variant 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 the hypothesis that over activity of AADC leading to increased production of 2PE is involved in endogenous psychosis such as schizophrenia.
Buckland
P R
PR
Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK. buckland@cardiff.ac.uk
Marshall
R
R
Watkins
P
P
McGuffin
P
P
D017398:Alternative Splicing; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000096:biosynthesis* / Q000235:genetics*; D001483:Base Sequence; D001921:Brain / Q000201:enzymology*; D002531:Cerebellum / Q000201:enzymology; D003342:Corpus Striatum / Q000201:enzymology; D005091:Exons; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D014644:Genetic Variation; D006624:Hippocampus / Q000201:enzymology; D006801:Humans; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D009714:Nucleus Accumbens / Q000201:enzymology; D015345:Oligonucleotide Probes; D010622:Phencyclidine / Q000494:pharmacology*; D010627:Phenethylamines / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000201:enzymology*; D017384:Sequence Deletion; D014158:Transcription, Genetic / Q000187:drug effects*
D015345:Oligonucleotide Probes; D010627:Phenethylamines; D012333:RNA, Messenger; C029261:phenethylamine; D008238:Lysergic Acid Diethylamide; D001142:Aromatic-L-Amino-Acid Decarboxylases; D010622:Phencyclidine