ASSESSMENT OF DELTA-OPIOID ANTINOCICEPTION AND RECEPTOR MESSENGER-RNALEVELS IN MOUSE AFTER CHRONIC NALTREXONE TREATMENT

The antinociceptive potency of the delta opioid receptor (DOR) agonist [D-Ala(2)]Deltorphin II and the levels of DOR mRNA were measured in m ice chronically treated with naltrexone. ED(50) determinations for [D- Ala(2)]Deltorphin II, using the tail-flick test with mice that had bee n treated with naltrexone for 7 days followed by a 24 h naltrexone fre e period (study day 8), revealed a 7.7-fold increase in antinociceptiv e potency, indicating functional supersensitivity, Utilization of a mi cro-dissection technique followed by quantitative solution hybridizati on measurements of RNA extracts from mouse CNS revealed levels of DOR mRNA ranging from 2.8 pg/mu g RNA in the caudate-putamen to 0.3 pg/mu g RNA in cerebellum. However, despite the functional increase in DOR s ensitivity, the DOR mRNA levels in selected brain areas and spinal cor d 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-tr eated and control mice revealed a similar pattern of results. Northern blot analysis of mouse whole brain RNA extracts after 7 days of naltr exone treatment did not show any alteration in the size of the DOR tra nscript. These data demonstrate that DOR mRNA levels are not altered d uring and after chronic naltrexone treatment and therefore are not ass ociated with opioid-induced DOR up-regulation or DOR functional supers ensitivity.