A comparison of morphine analgesic tolerance in male and female mice

Kest, Benjamin; Palmese, Christina A.; Hopkins, Eileen

doi:10.1016/s0006-8993(00)02685-8

Cited by 54 publications

(26 citation statements)

References 35 publications

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“…Our result is in accord with previous studies that observed similar sex-related differences in development of morphine tolerance (Badillo-Martinez et al, 1984; Craft et al, 1999; South et al, 2001; Loyd et al, 2008). However, this difference was not noted in other reports (Kest et al, 2000; Barrett et al, 2001; Holtman et al, 2004). Our study utilized a relatively high dose (10–80 mg/kg, twice daily for 5 days) of morphine that likely induced greater tolerance than other paradigms, and challenged with only a single, moderate morphine dose.…”

Section: Discussioncontrasting

confidence: 70%

“…The other study suggested that when the functional chronic morphine dose (chronic morphine dose/acute morphine potency) was adjusted, the development of morphine tolerance was comparable in male and female Lewis and F344 rats (Barrett et al, 2001). In contrast to rats, female mice undergo greater reductions in morphine analgesia relative to males following chronic morphine (Kest et al, 2000). Therefore, it seems that morphine dose, species and method of pain measurement account for the discrepancy.…”

Section: Discussionmentioning

confidence: 99%

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Sex differences in the Nociceptin/Orphanin FQ system in rat spinal cord following chronic morphine treatment

2012

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Nociceptin/Orphanin FQ (N/OFQ) appears to contribute to the development of morphine tolerance, as blockade of its actions will block or reverse the process. To better understand the contribution of N/OFQ to the development of morphine tolerance, this study examined the effect of chronic morphine treatment on levels of N/OFQ and levels and activity of the N/OFQ peptide (NOP) receptor in spinal cord (SC) from male and female rats. Both male and female Wistar rats showed less responsiveness to morphine after subcutaneous injection of escalating doses of morphine (10, 20, 40, 60 and 80 mg/kg, respectively) twice daily for five consecutive days. Male rats were more tolerant to the antinociceptive actions of morphine than females. The N/OFQ content of SC extracts was higher in females than in males, regardless of treatment; following chronic morphine treatment the difference in N/OFQ levels between males and females was more pronounced. N/OFQ content in cerebrospinal fluid (CSF) was reduced 40% in male and 16% in female rats with chronic morphine exposure, but increased in periaqueductal grey of both sexes. Chronic morphine treatment increased NOP receptor levels 173% in males and 137% in females, while decreasing affinity in both. Chronic morphine increased the efficacy of N/OFQ-stimulated [35S]GTPγS binding to SC membranes from male rats, consistent with increased receptor levels. Taken together, these findings demonstrate sex differences in N/OFQ–NOP receptor expression and NOP receptor activity following chronic morphine treatment. They also suggest interplay between endogenous N/OFQ and chronic morphine treatment that results in nociceptive modulation.

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Section: Discussioncontrasting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Sex differences in the Nociceptin/Orphanin FQ system in rat spinal cord following chronic morphine treatment

2012

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“…These reports also showed that U50488H, a selective KOP receptor agonist, and other opioids (e.g., U69593, bremazocine, and butorphanol) are more effective in males than in females. Furthermore, with regard to MOP receptor-selective agonists, morphine exerted greater antinociceptive effects in male than in female mice [29], rats [30,31], and monkeys [32]. Additionally, female mice may differentially respond in pain tests during different phases of their estrous cycle [18].…”

Section: Discussionmentioning

confidence: 99%

(−)-Pentazocine Induces Visceral Chemical Antinociception, but not Thermal, Mechanical, or Somatic Chemical Antinociception, in μ-Opioid Receptor Knockout Mice

et al. 2011

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Background(-)-Pentazocine has been hypothesized to induce analgesia via the κ-opioid (KOP) receptor, although the involvement of other opioid receptor subtypes in the effects of pentazocine remains unknown. In this study, we investigated the role of the μ-opioid (MOP) receptor in thermal, mechanical, and chemical antinociception induced by (-)-pentazocine using MOP receptor knockout (MOP-KO) mice.Results(-)-Pentazocine-induced thermal antinociception, assessed by the hot-plate and tail-flick tests, was significantly reduced in heterozygous and abolished in homozygous MOP-KO mice compared with wildtype mice. The results obtained from the (-)-pentazocine-induced mechanical and somatic chemical antinociception experiments, which used the hind-paw pressure and formalin tests, were similar to the results obtained from the thermal antinociception experiments in these mice. However, (-)-pentazocine retained its ability to induce significant visceral chemical antinociception, assessed by the writhing test, in homozygous MOP-KO mice, an effect that was completely blocked by pretreatment with nor-binaltorphimine, a KOP receptor antagonist. In vitro binding and cyclic adenosine monophosphate assays showed that (-)-pentazocine possessed higher affinity for KOP and MOP receptors than for δ-opioid receptors.ConclusionsThe present study demonstrated the abolition of the thermal, mechanical, and somatic chemical antinociceptive effects of (-)-pentazocine and retention of the visceral chemical antinociceptive effects of (-)-pentazocine in MOP-KO mice. These results suggest that the MOP receptor plays a pivotal role in thermal, mechanical, and somatic chemical antinociception induced by (-)-pentazocine, whereas the KOP receptor is involved in visceral chemical antinociception induced by (-)-pentazocine.

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“…Male and female mice (31,37) and rats (4,17,35,60) can differ in the degree of morphine tolerance. In some cases, the greater sensitivity of males to acute morphine analgesia could account for the greater tolerance observed in male rats (6) or in female rats at a particular phase of the estrous cycle (56).…”

Section: Discussionmentioning

confidence: 99%

NMDA receptor antagonism disrupts the development of morphine analgesic tolerance in male, but not female C57BL/6J mice

Bryant

Eitan²,

Sinchak

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Multiple studies demonstrate that coadministration of N-methyl-D-aspartate (NMDA) receptor antagonists with the opioid agonist morphine attenuates the development of analgesic tolerance. Sex differences in the effects of noncompetitive, but not competitive NMDA receptor antagonists on acute morphine analgesia, have been reported in mice, yet the role of sex in modulation of morphine tolerance by NMDA receptor antagonists has yet to be addressed. Therefore, we tested whether there is a sex difference in the effect of NMDA receptor antagonists on the development of morphine analgesic tolerance in C57BL/6J mice. Acutely, at a dose required to affect morphine tolerance in male mice, the noncompetitive NMDA receptor antagonist dizocilpine (MK-801) prolonged morphine analgesia similarly in both sexes in the hot plate and tail withdrawal assays. In the hot plate assay, coadministration of MK-801 or the competitive antagonist 3-(2-carboxpiperazin-4-yl)propyl-1-phosphanoic acid (CPP) with morphine attenuated the development of tolerance in male mice, while having no effect in females. Like normal and sham females, ovariectomized mice were similarly insensitive to the attenuation of morphine tolerance by MK-801 in the hot plate assay. Surprisingly, in the tail withdrawal assay, MK-801 facilitated the development of morphine-induced hyperalgesia and tolerance in males but not females. The results demonstrate that male mice are more sensitive to modulation of nociception and morphine analgesia after repeated coadministration of NMDA receptor antagonists. Furthermore, the underlying mechanisms are likely to be different from those mediating the sex difference in the modulation of acute morphine analgesia that has previously been reported.

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A comparison of morphine analgesic tolerance in male and female mice

Cited by 54 publications

References 35 publications

Sex differences in the Nociceptin/Orphanin FQ system in rat spinal cord following chronic morphine treatment

Sex differences in the Nociceptin/Orphanin FQ system in rat spinal cord following chronic morphine treatment

(−)-Pentazocine Induces Visceral Chemical Antinociception, but not Thermal, Mechanical, or Somatic Chemical Antinociception, in μ-Opioid Receptor Knockout Mice

NMDA receptor antagonism disrupts the development of morphine analgesic tolerance in male, but not female C57BL/6J mice

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