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.

Abstract:

: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.

journal_name

Br J Pharmacol

authors

Bhargava HN

doi

10.1111/j.1476-5381.1981.tb09152.x

subject

Has Abstract

pub_date

1981-04-01 00:00:00

pages

707-14

issue

4

eissn

0007-1188

issn

1476-5381

journal_volume

72

pub_type

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