The effect of melanotrophin release inhibiting factor (MIF) and cyclo (Leu-Gly) on the tolerance to morphine-induced antinociception in the rat: a dose-response study.
1. The effects of melanotrophin release inhibiting factor (MIF) and its cyclic analogue cyclo (Leu-Gly) on tolerance to the analgesic effect of morphine were studied in male Sprague-Dawley rats. 2. Tolerance to morphine was induced by implantation of four morphine pellets (each containing 75 mg of morphine free base) during a 3 day period. 3. Daily subcutaneous administration of MIF and cyclo (Leu-Gly) before and during the morphine pellet implantation inhibited the development of tolerance to morphine analgesia. The minimum daily dose of the peptides required to produce a significant effect was 0.5 mg/kg. 4. The effects of single injections of MIF and cyclo (Leu-Gly) on morphine tolerance revealed that the minimum doses of cyclo (Leu-Gly) and MIF to inhibit morphine tolerance were 4 and 8 mg/kg, respectively. 5. Chronic treatment with morphine resulted in an enhanced hypothermic response to dopamine agonist, apomorphine. The enhancement of this response was blocked by both MIF and cyclo (Leu-Gly) in doses that inhibited morphine tolerance. 6. It is concluded that MIF and cyclo (Leu-Gly) blocked the development of analgesic tolerance as well as dopamine receptor hypersensitivity induced by chronic morphine treatment and the two phenomena may be interrelated.
D000698:Analgesia; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D007035:Hypothermia / Q000139:chemically induced; D009075:MSH Release-Inhibiting Hormone / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009479:Neuropeptides; D010456:Peptides, Cyclic; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects
D004151:Dipeptides; D009479:Neuropeptides; D010456:Peptides, Cyclic; D011954:Receptors, Dopamine; C021166:cyclo(leucylglycine); D009020:Morphine; D009075:MSH Release-Inhibiting Hormone; D001058:Apomorphine