The development and reversal of the tolerance to morphine in the longitudinal smooth muscle-myenteric plexus preparation of the guinea pig

Leedham, Judith A.; Doak, Nancy; Taylor, David A.; Fleming, William W.

doi:10.1016/0024-3205(89)90039-8

Cited by 6 publications

(7 citation statements)

References 5 publications

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“…This effect has not previously been reported though Li et al (2010) did observe a significant reduction in responsiveness beyond 14 days that spontaneously resolved by 21 days. The data provided in this study differ from those described by Leedham et al (1989) who found total reversal of tolerance at 14 days. Though no explanation is immediately apparent for the difference in these results, it is certainly possible that the development of tolerance beyond 14 days could well be a function of the sample size.…”

Section: Discussioncontrasting

confidence: 99%

“…The calculated magnitude of rightward or loss of sensitivity shift (i.e., ratio of mean IC 50 values) of the treated compared to the control group was nearly fourfold for DAMGO and threefold for CADO at 4 days and reached a maximum of seven- to eightfold for both agonists 7 and 10 days after treatment (Tables 1 and 2). In addition, the maximum inhibitory effect for each agonist (ranged from 85 ± 5 to 100% of the twitch amplitude) at each time period and was not statistically significantly different between the treatment groups as has been previously reported (Leedham et al, 1989). …”

Section: Resultssupporting

confidence: 80%

“…The development of tolerance to the action of DAMGO and 2-CADO on neurogenic twitches of the LM/MP has been reported in several different studies (Taylor et al, 1988; Leedham et al, 1989; Li et al, 2010). While most investigators use a 7-day treatment period, only a few have conducted extensive time course studies to characterize the functional changes in responsiveness (Leedham et al, 1989; Li et al, 2010).…”

Section: Discussionmentioning

confidence: 77%

“…While most investigators use a 7-day treatment period, only a few have conducted extensive time course studies to characterize the functional changes in responsiveness (Leedham et al, 1989; Li et al, 2010). The data generated in this current study confirm the previous results and additionally demonstrates that the change in responsiveness to 2-CADO persisted well beyond the 14-day time period.…”

Section: Discussionmentioning

confidence: 99%

“…However, no studies have evaluated the time course of the development of the change in responsiveness to determine whether the enhanced responsiveness shared a similar onset and decay as that observed for inhibitory agents (Leedham et al, 1989; Li et al, 2010). The observation that changes in cellular responsiveness to the excitatory effect of nicotine develop over a similar time course to the reduced responsiveness to both DAMGO and CADO in the LM/MP preparation further reinforces the idea that the adaptive change following chronic morphine treatment involves a modification in the membrane potential of myenteric “S” neurons (Meng et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

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Time Course of Altered Sensitivity to Inhibitory and Excitatory Agonist Responses in the Longitudinal Muscle–Myenteric Plexus and Analgesia in the Guinea Pig after Chronic Morphine Treatment

Barrett¹,

Maguma²,

Taylor³

2012

Front. Pharmacol.

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Tolerance that develops after chronic morphine exposure has been proposed to be an adaptive response that develops and decays over a defined time course. The present study examined the development of tolerance to the acute hypothermic and analgesic effects of morphine and correlated the time course for the desensitization in vivo with the reduced responsiveness to DAMGO and 2-CADO and increased responsiveness to nicotine of the longitudinal muscle/myenteric plexus (LM/MP) preparation in vitro. Assessment was performed at various times after morphine or placebo pellet implantation. Morphine produced a modest hypothermic response to which no tolerance developed. However, the development of tolerance to the analgesic effect of morphine, the inhibitory effect of DAMGO and CADO on neurogenic twitches of the LM/MP and hypersensitivity to the contractile response to nicotine was observed to occur in a time-dependent manner. The alterations in sensitivity to DAMGO, nicotine, and responsiveness to morphine analgesia occurred between days 4 and 10 and returned to normal by day 14 post-implantation. In contrast, sensitivity of LM/MP preparations to 2-CADO displayed a similar time-dependent onset but the tolerance persisted beyond 14 days after implantation. These data suggest that the heterologous tolerance that develops after chronic morphine treatment is time-dependent and persistent but, ultimately returns to normal in the absence of any intervention. Furthermore, the data suggest that the basis of the adaptive phenomenon may involve multiple cellular mechanisms including the modulation of cell excitability and normal physiology but the consequences of the adaptation extend to all effects of the agonist.

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Section: Discussioncontrasting

confidence: 99%

Section: Resultssupporting

confidence: 80%