Assessment of delta opioid antinociception and receptor mRNA levels in mouse after chronic naltrexone treatment.
The antinociceptive potency of the delta opioid receptor (DOR) agonist [D-Ala2]Deltorphin II and the levels of DOR mRNA were measured in mice chronically treated with naltrexone. ED50 determinations for [D-Ala2]Deltorphin II, using the tail-flick test with mice that had been treated with naltrexone for 7 days followed by a 24 h naltrexone free period (study day 8), revealed a 7.7-fold increase in antinociceptive potency, indicating functional supersensitivity. Utilization of a micro-dissection technique followed by quantitative solution hybridization measurements of RNA extracts from mouse CNS revealed levels of DOR mRNA ranging from 2.8 pg/microgram RNA in the caudate-putamen to 0.3 pg/microgram RNA in cerebellum. However, despite the functional increase in DOR sensitivity, the DOR mRNA levels in selected brain areas and spinal cord of naltrexone-treated and control mice did not differ. Assessment of DOR mRNA levels in whole brain and selected CNS regions after shorter treatment intervals (1, 6 and 12 h and 2 and 7 days) in naltrexone-treated and control mice revealed a similar pattern of results. Northern blot analysis of mouse whole brain RNA extracts after 7 days of naltrexone treatment did not show any alteration in the size of the DOR transcript. These data demonstrate that DOR mRNA levels are not altered during and after chronic naltrexone treatment and therefore are not associated with opioid-induced DOR up-regulation or DOR functional supersensitivity.
Jenab
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Department of Pharmacology, Cornell University Medical College, New York, NY 10021, USA.
Kest
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B
Inturrisi
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CE
D000818:Animals; D015152:Blotting, Northern; D005069:Evaluation Studies as Topic; D008297:Male; D051379:Mice; D009271:Naltrexone / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000819:agonists*; D013997:Time Factors
D009842:Oligopeptides; D012333:RNA, Messenger; D017465:Receptors, Opioid, delta; C060209:deltorphin II, Ala(2)-; D009271:Naltrexone