Abstract
We examined whether mu-antisense (AS) oligodeoxynucleotide (oligo) treatment can be used in a manner similar to the mu-selective irreversible antagonist beta-funaltrexamine (beta-FNA) for in vivo pharmacology. Rats were injected intracerebroventricularly (icv) with a mu-AS or a missense (MS) oligo on days 1, 3, 5, 7, and 9 and were tested for the antinociceptive effect of sc injection of morphine on days 2, 4, 6, 8, and 10 in the cold water tail-flick (CWT) test. In another set of experiments, rats were also tested for the antinociceptive action of morphine twenty-four hours after icv injection of beta-FNA. Both beta-FNA and mu-AS produced rightward shifts in the dose-effect curves of morphine. In addition, pretreatment with 2.5 micrograms or more of beta-FNA or the mu-AS oligo for 5-9 days (but not for 1-3 days) reduced the maximal analgesic effect of morphine. The approximate fraction of functional receptor remaining for morphine was determined with the method of Furchgott to be 49.5% following 2.5 micrograms of beta-FNA; that after 5 days of the mu-AS oligo treatment was 50.8%. The results suggest that the mu-AS oligo can be used in the same manner as highly selective, irreversible mu opioid receptor ligands. Thus, properly ...Continue Reading
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