PMID: 8584751Oct 20, 1995Paper

Antisense oligonucleotide inhibition of tryptophan hydroxylase activity in mouse brain

Regulatory Peptides
M M McCarthyD Goldman

Abstract

To examine in vivo effectiveness of antisense oligonucleotides against tryptophan hydroxylase (TPH) mRNA, adult male swiss-NIH mice were implanted with in-dwelling cannula into the 4th ventricle and after recovery infused with either antisense oligonucleotide to TPH, scrambled control oligo or saline vehicle for four consecutive days. An additional group of animals bearing cannula were injected a single time i.p. with the TPH inhibitor para-chlorophenylalanine (PCPA; 300 mg/kg). All animals were sacrificed on the afternoon of the 4th day of treatment. TPH activity was measured by enzymatic assay and HPLC quantification of end-product synthesis. There was a significant decrease (> 50%) in TPH activity in both the PCPA-treated and antisense-oligo infused animals compared to either scrambled-oligo or saline-infused subjects (ANOVA; P < 0.05). There was no difference between saline and scrambled oligo-infusion. In a separate group of animals treated in the same way, behavioral tests were conducted on the afternoon of the 4th day. Two tests of anxiety, the hole-board apparatus and the elevated plus-maze, indicated some significant effects of PCPA treatment and/or antisense oligo-infusion but confounding effects due to alterations in...Continue Reading

References

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Citations

Jun 15, 1999·Trends in Pharmacological Sciences·D L MurphyA Heils
Sep 1, 1997·Neurochemistry International·B WeissS P Zhang
Oct 13, 2001·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·M W Gittos, M Papp
Mar 12, 2004·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Yukiko HorinouchiHaruo Nagayama
Jan 10, 2001·Developmental Psychobiology·L A HydeP C Bickford
Apr 7, 1999·Antisense & Nucleic Acid Drug Development·A W Szklarczyk, L Kaczmarek

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