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Time Course of Altered Sensitivity to Morphine‐induced Analgesia in the Guinea Pig and Inhibitory and Excitatory Agonist Responses in the Longitudinal Muscle‐Myenteric Plexus after Chronic Morphine Treatment
Author(s) -
Barrett Dane M,
Maguma Hercules T,
Taylor David A
Publication year - 2011
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.25.1_supplement.618.4
Subject(s) - myenteric plexus , morphine , excitatory postsynaptic potential , inhibitory postsynaptic potential , agonist , guinea pig , pharmacology , medicine , anesthesia , endocrinology , receptor , immunohistochemistry
Heterologous tolerance that develops after chronic morphine exposure has been proposed to be an adaptive response that develops and decays over a time course consistent with the cellular changes that are responsible. The present study correlated the development of reduced analgesic response to morphine in vivo with reduced neurogenic twitch inhibition by DAMGO and 2‐chloroadenosine (CADO) and increased nicotine‐induced contractions of longitudinal muscle/myenteric plexus (LM/MP) preparations. Assessment was done at various times after morphine or placebo pellet implantation. The analgesic effect produced by morphine and the inhibitory effect of DAMGO and CADO on neurogenic twitches of the LM/MP were reduced in a time‐dependent manner following implantation. Similarly, the contractile response to nicotine was increased in a time‐dependent manner. Alterations in responsiveness were observed at day 4 post‐implantation, reached maximum by day 7 and returned to normal by day 14 for analgesia and nicotine‐induced contractions. The responsiveness of LM/MP preparations to all agonists except CADO returned to normal levels by day 21 indicating a spontaneous return of responsiveness. These data suggest that the persistent heterologous tolerance that develops after chronic morphine treatment may involve multiple cellular mechanisms including the modulation of cell excitability and normal physiology.