Premium
The influence of the route of chronic administration of morphine on the expression of tolerance in the guinea‐pig ileum
Author(s) -
Li Peng,
Thayne Kathleen,
Davis Barbara,
Taylor David A.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a411-c
Subject(s) - morphine , pellet , medicine , drug tolerance , anesthesia , biology , zoology
Subcutaneous (s.c.) pellet implantation is a technique widely used to induce tolerance to opioids. However, few studies have compared tolerance produced by pellet implantation with that produced by methods of administration more closely aligned with the clinical use of morphine. The present study compared the expression of tolerance following morphine pellet implantation with chronic parenteral injection. Two dosing schemes for s.c. pellet implantation included one in which guinea‐pigs were implanted once with morphine or placebo pellets either 4 or 7 days before the experiment and another involving escalating multiple pellet implantations over 7 days. The two parenteral schemes used s.c. injection over a short‐term aggressive exposure period and a less aggressive 7 day exposure period. The characteristics of tolerance were measured by the loss in responsiveness of the longitudinal muscle myenteric/plexus preparation to the neurogenic twitch inhibition produced by morphine, DAMGO and 2‐chloroadenosine. Tolerance was observed following all forms of administration to all agonists. The single pellet implantation produced a 2–5‐fold reduction in responsiveness at 4 days and a 3–5‐fold reduction in responsiveness at 7 days while multiple pellet implantation produced a 2–3‐fold reduction in responsiveness at 7 days. Both injection procedures produced a 2.5–4.5‐fold reduction in responsiveness at after either 4 or 7 days of treatment. The results from the present study indicate that either subcutaneous pellet implantation or injection of morphine produces tolerance that is qualitatively and quantitatively similar, and that tolerance produced by chronic exposure to morphine in the guinea‐pig is not dependent upon the route of administration.