Morphine analgesic tolerance in 129P3/J and 129S6/SvEv mice

Abstract

Morphine analgesic tolerance is heritable in both humans and rodents, with some individuals and strains exhibiting little and others exhibiting robust tolerance. 129S6/SvEv and 129P3/J mice reportedly do not demonstrate tolerance to morphine analgesia. Using our laboratory's standard morphine tolerance regimen and a between-subjects design, tolerance developed in the hot plate and tail withdrawal assays as indicated by a change in analgesic efficacy following a morphine challenge dose. Furthermore, the non-competitive NMDA receptor antagonist MK-801 (dizocilipine) blocked morphine tolerance in 129S6/SvEv and CD-1 mice in the hot plate assay. As previously reported, when a within-subjects design and cumulative dosing was employed, no tolerance was observed in the 129P3/J strain. However, using the same morphine regimen and a between-subjects design, comparable tolerance developed between 129P3/J and C57BL/6J strains following a single challenge dose of morphine. Spontaneous hyperalgesia was observed in the tail withdrawal assay following chronic morphine in C57BL/6J, but not 129P3/J mice. Additionally, morphine-tolerant C57BL/6J mice, but not 129P3/J mice, exhibited a large increase in the frequency of tail flicks during the first second following the baseline nociceptive response which may facilitate detection of the response during the tolerant state. We conclude that the method of tolerance assessment affects the ability to detect tolerance and thus, may affect the degree and pattern of heritability of this trait and this could have implications for gene mapping studies.

Casein kinase 1‐epsilon deletion increases mu opioid receptor‐dependent behaviors and binge eating1

“…Baseline hot plate latency was analyzed via two-way ANOVA (Sex, Genotype) followed by post-hoc Welch's t-test to identify the effect of Genotype. We measured fentanyl analgesia using Percent Maximum Possible Effect (%MPE; Bryant et al 2006). We analyzed FENT analgesia via three-way ANOVA (Sex, Genotype, Dose), followed by a post-hoc two-way ANOVA with Genotype and Dose as factors.…”

“…We measured fentanyl analgesia using Percent Maximum Possible Effect (%MPE) (Bryant et al ., 2006). We analyzed FENT analgesia via three-way ANOVA (Sex, Genotype, Dose), followed by a post-hoc two-way ANOVA with Genotype and Dose as factors.…”

“…We used the 52.5 ∘ hot plate assay to assess baseline nociception and fentanyl-induced analgesia (Bryant et al 2006). We habituated mice to the testing room for at least 1 h. We then placed mice in a Plexiglas cylinder (15 cm diameter; 33.0 cm tall) on a hot plate (IITC Life Science Inc., Woodland Hills, CA, USA) and recorded the latency to lick the hind paw with a 60-second cut-off latency.…”

Naloxone-precipitated morphine withdrawal behavior and brain IL-1β expression: Comparison of different mouse strains

“…Studies of morphine analgesic tolerance utilizing wild-type inbred strains have shown substantial shifts to the right in the dose-response curve of Balb/c, CBA, and C57BL/6 mice, however, there is no change in analgesic efficacy at lower morphine doses (< 10 mg/kg) for C57BL/6 and CBA mice (Bryant et al, 2006; Kest et al, 2002a; Liang et al, 2006a). In the current study, by using a single morphine challenge dose (7.5 mg/kg), only wild-type Balb/c mice exhibited analgesic tolerance, but not CBA and C57BL/6 mice, which supports previous findings.…”

Endogenous opiates and behavior: 2009

“…Organismic effects on morphine tolerance-Antinociceptive tolerance was observed following cumulative intracranial microinjections of morphine into the PAG in the rat (795). Morphine analgesic tolerance in 129P3/J and 129S6/SvEv mice was largely absent because of differences in tail-flick responsivity between these strains and C57BL/6J mice (148). Acute morphine tolerance was observed in proestrous, but not ovariectomized female rats; chronic estradiol in ovariectomized animals reinstated acute morphine tolerance.…”