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Assessing the decay of heterologous tolerance to morphine after varying lengths of treatment via intraperitoneal (I.P.) injection
Author(s) -
Thompson Ben G,
Masterson Jackie M,
Taylor David A
Publication year - 2013
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.27.1_supplement.886.4
Subject(s) - morphine , drug tolerance , heterologous , medicine , pain tolerance , cross tolerance , anesthesia , pharmacology , chemistry , threshold of pain , biochemistry , gene
The development and decay of heterologous tolerance following chronic morphine exposure via pellet implantation is well documented in the guinea pig longitudinal muscle/myenteric plexus (LM/MP). However, this method of administration only permits a qualitative analysis of the decay of tolerance because the time at which morphine exposure is completed is unknown. Therefore, we assessed the decay of tolerance in animals pretreated with twice daily i.p. injections of morphine for 4 or 7 days. Tolerance to the analgesic effects of morphine was assessed using the paw pressure test while the heterologous nature of tolerance was evaluated using the response of the LM/MP to DAMGO and 2‐CADO at 0, 1, 2, or 4 days after treatment cessation. The data indicated that the time for return to baseline was correlated to the magnitude of tolerance that was a function of the length of treatment. The tolerance generated in animals treated for 4 days was nearly 4‐fold and decayed to baseline within 2 days after the treatment ended while tolerance observed in animals treated for 7 days was nearly 6‐fold and returned to baseline levels 4 days after treatment cessation. The fact that the decay of tolerance is a function of both the length of treatment and magnitude of tolerance developed reinforces the idea that tolerance following chronic treatment with morphine is an adaptive process produced by alterations in several cellular signaling proteins.