Journal article
Intraperitoneal injection of antisense peptide nucleic acids targeted to the mu receptor decreases response to morphine and receptor protein levels in rat brain
Brain research, v 904(2), pp 345-349
22 Jun 2001
PMID: 11406133
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
To determine the effectiveness of peptide nucleic acids (PNAs) in vivo, we designed and synthesized PNAs antisense to the mu receptor, the molecular target of morphine for inducing antinociception. Responsiveness of rats to morphine and the levels of mu receptor expression after treatment was measured. We delivered intraperitoneal injections of antisense PNAs targeted to the mu receptor (AS-MOR), mismatch PNAs (AS-MOR MM), antisense PNAs targeted to the neurotensin receptor subtype 1 (AS-NTR1), or saline and then challenged the rats with 5 mg/kg morphine (intraperitonally) or neurotensin directly into the periaqueductal gray region of the brain. To avoid tolerance, separate groups of animals were tested at 24, 48, and 72 h post-PNA treatment. Only animals treated with the AS-MOR showed a reduction in their antinociceptive response to morphine. The lack of effect of morphine on the AS-MOR rats was profound at 24 and 48 h, but animals tested at 72 h were similar to control groups. At 24 h the AS-MOR rats had a significant 55% decrease in the levels of mu receptor in their periaqueductal gray region, while AS-MOR MM rats showed no significant change. Lastly, the AS-MOR rats continued to show a normal antinociceptive response to neurotensin. This study, therefore, provides additional support for the use of PNAs to target proteins within brain by systemically administered PNAs.
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Details
- Title
- Intraperitoneal injection of antisense peptide nucleic acids targeted to the mu receptor decreases response to morphine and receptor protein levels in rat brain
- Creators
- Beth M. McMahon - Mayo Clinic in FloridaJennifer A. Stewart - Mayo ClinicJoshua Jackson - Mayo ClinicAbdul Fauq - Mayo ClinicDaniel J. McCormick - Mayo ClinicElliott Richelson - Mayo Clinic
- Publication Details
- Brain research, v 904(2), pp 345-349
- Publisher
- Elsevier
- Number of pages
- 5
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000169589000018
- Scopus ID
- 2-s2.0-0035933505
- Other Identifier
- 991021900018704721
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- Web of Science research areas
- Neurosciences