D-2 DOPAMINE-RECEPTOR ANTISENSE INCREASES THE ACTIVITY AND MESSENGER-RNA OF TYROSINE-HYDROXYLASE AND AROMATIC L-AMINO-ACID DECARBOXYLASE INMOUSE-BRAIN

A D-2 dopamine receptor antisense oligodeoxynucleotide was administere d intracerebrovetricularly to mice twice on the first day and then onc e daily for 2 days. The animals were killed 2 h after the last injecti on, and tyrosine hydroxylase and aromatic L-amino acid decarboxylase a ctivities assayed in the corpus striatum, olfactory tubercle and front al cortex. Tyrosine hydroxylase activity increased in corpus striatum but not in the olfactory tubercle or in the frontal cortex, while the activity of aromatic L-amino acid decarboxylase increased in all three brain regions. The treatment with the antisense oligomer also elevate d the mRNA levels for the two enzymes in the midbrain. In contrast, re peated injection of a vehicle or a random oligomer was without effect on enzyme activity or mRNA D-2 antisense oligodeoxynucleotides appear to be selective tools to investigate the role of D-2 dopamine receptor s in brain.