Amphetamine and vigabatrin down regulate aromatic L-amino acid decarboxylase mRNA levels.
Aromatic L-amino acid decarboxylase (AADC) has previously been shown to be up-regulated at the level of its protein activity and its mRNA abundance by antipsychotic drugs. Its activity has also been shown to be down-regulated by dopamine agonists including amphetamine. In this study we have injected rats for up to 32 days with amphetamine and the anti-epileptic drug vigabatrin, both of which can cause psychosis with similarities to schizophrenia. We have shown that AADC mRNA levels are reduced in most brain regions by both drugs. Cocaine and other non-psychotogenic anti-epileptic drugs had no effect in this paradigm. Two products of this enzyme are implicated in psychotogenesis.
Buckland
P R
PR
Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK.
Spurlock
G
G
McGuffin
P
P
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000096:biosynthesis*; D001483:Base Sequence; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D009928:Organ Specificity; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D014635:Valproic Acid / Q000494:pharmacology; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D000661:Amphetamine; D001142:Aromatic-L-Amino-Acid Decarboxylases; D020888:Vigabatrin