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An antisense oligodeoxynucleotide to mu-opioid receptors inhibits mu-opioid receptor agonist-induced analgesia in rats. 1995

X H Chen, and J U Adams, and E B Geller, and J K DeRiel, and M W Adler, and L Y Liu-Chen
Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA.

We examined effects of an antisense oligodeoxynucleotide against the mu-opioid receptor on mu-opioid receptor agonist-induced antinociception in the cold water (-3 degrees C) tail-flick test in rats. Rats were injected intracerebroventricularly (i.c.v.) with an antisense, sense or missense oligodeoxynucleotide or artificial cerebrospinal fluid on days 1, 3 and 5. On day 6, antinociceptive effects of opioid agonists were tested. Compared to the artificial cerebrospinal fluid treatment, the cumulative dose-effect curve for subcutaneous (s.c.) morphine was shifted to the right by the antisense oligodeoxynucleotide, but not by the missense oligodeoxynucleotide or the sense oligodeoxynucleotide treatment. Antisense oligodeoxynucleotide treatment reduced the analgesic effect of the mu-opioid receptor agonist PL017 ([N-MePhe3,D-Pro4]morphiceptin), but not the delta-opioid receptor agonist BW373U86 ((+/-)-4-((a-R*)-a-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl)-3- hydroxybenzyl)-N,N-diethyl-benzamide) or the kappa-opioid receptor agonist spiradoline ((+/-)-(5a,7a,8b)-3,4-dichloro-N-methyl-N-[7-(1- pyrrolidinyl)-1-(oxaspiro-[4,5]dec-8-yl]benzeneacetamide monohydrochloride). The drugs were given by i.c.v. injection. These findings indicate that i.c.v. administration of a mu antisense oligodeoxynucleotide specifically blocks mu-, but not delta- or kappa-opioid receptor-mediated analgesia in the rat cold water tail-flick test.

UI MeSH Term Description Entries
D007276 Injections, Intraventricular Injections into the cerebral ventricles. Intraventricular Injections,Injection, Intraventricular,Intraventricular Injection
D007279 Injections, Subcutaneous Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin. Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D008297 Male Males
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009020 Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D011759 Pyrrolidines Compounds also known as tetrahydropyridines with general molecular formula (CH2)4NH. Tetrahydropyridine,Tetrahydropyridines
D011897 Random Allocation A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. Randomization,Allocation, Random
D002555 Cerebrospinal Fluid A watery fluid that is continuously produced in the CHOROID PLEXUS and circulates around the surface of the BRAIN; SPINAL CORD; and in the CEREBRAL VENTRICLES. Cerebro Spinal Fluid,Cerebro Spinal Fluids,Cerebrospinal Fluids,Fluid, Cerebro Spinal,Fluid, Cerebrospinal,Fluids, Cerebro Spinal,Fluids, Cerebrospinal,Spinal Fluid, Cerebro,Spinal Fluids, Cerebro
D004723 Endorphins One of the three major groups of endogenous opioid peptides. They are large peptides derived from the PRO-OPIOMELANOCORTIN precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; OPIOID PEPTIDES is used for the broader group. Endorphin

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