ArticlesKappa Antinociceptive Activity of Spiradoline in the Cold-Water Tail-Flick Assay in Rats
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Subjects
Male Sprague–Dawley rats, weighing 300 to 500 g, were approved for use in the following experiments by the All-University Committee on Animal Use and Care of Michigan State University. All rats were trained over a 2-month period to lie quietly in a towel that was snugly secured around them. Training started for rats between the ages of 60 to 80 days. After approximately 6 weeks of training, rats accommodated to being restrained in the towels without struggling. The subjects were reinforced
Dose–Response Patterns of the Agonists in CWTF
Results of log dose–response analyses in the CWTF demonstrated that spiradoline acted as a full agonist in producing antinociception with an AD50 of 0.56 mg/kg SC (Fig. 1B). This result is in good agreement with those of spiradoline tested in other nociceptive assays in the rat (26). However, the dose–response analysis of spiradoline was somewhat limited in that higher doses also produced behaviors that tended to confound observations. For reporting of accurate observations, subjects had to
Discussion
The dose–response curves of fentanyl and spiradoline described above indicate that mu and kappa agonists can be equally efficacious as antinociceptives in the CWTF at −10°C. Spiradoline appears to act as a full agonist in the CWTF at −10°C and appears to produce its antinociceptive effect by selective action at kappa receptors. It is important to note that this study used a 60-s latency cutoff, which has been shown to separate strong narcotic analgesics from mixed agonist-antagonist drugs (21).
Acknowledgements
The authors wish to thank Ms. Stephanie Gollakner for her excellent skills and experience in animal handling and training and for her assistance in carrying out these experiments.
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Antinociceptive interactions of mu- and kappa-opioid agonists in the colorectal distension assay in rats
2009, Pharmacology Biochemistry and BehaviorCitation Excerpt :However, the score of the combined drugs after n-BNI was much reduced from those of saline-pretreatment rats (18% vs. 68% at the 15-min test, and 13% vs. 38% at the 30-min test). To emphasize the difference of the paradoxical effects in Fig. 4 compared to our results of agonist/antagonist interactions in the CWTF (Briggs et al., 1998a), the results from the CWTF study are repeated here. Using the CWTF, the mean MPE of fentanyl was 86% and that of spiradoline was 77% after saline pretreatment.
Placenta ingestion by rats enhances δ- and κ-opioid antinociception, but suppresses μ-opioid antinociception
2004, Brain ResearchCitation Excerpt :Furthermore, the κ-receptor-specific nature of spiradoline antinociception can be asserted on the basis of its reversibility by κ-selective antagonism. This has been demonstrated both with conventional pharmacological strategies and with molecular (antisense) techniques [4,8,60]. These results indicate that the antinociceptive effects of spiradoline are mediated exclusively at the κ receptor, and together with evidence that POEF decreases the μ antinociception generated by DAMGO (Experiment 2), make it very likely that the enhancing action of POEF on antinociception induced by the low dose of spiradoline represents a κ, and not a μ, effect.
Chronic sucrose intake augments antinociception induced by injections of mu but not kappa opioid receptor agonists into the periaqueductal gray matter in male and female rats
2001, Brain ResearchCitation Excerpt :The finding that spiradoline had only modest analgesic activity was not totally unexpected. Although spiradoline and other kappa agonists have been reported to have significant antinociceptive actions on variety of tests of pain sensitivity [5,7,8,21,24,31,34,38,47,49], kappa opioid agonists generally have been found to be less efficacious analgesics than mu agonists [8,24,34]. Moreover, it has been reported that kappa opioid agonists such as U50,488H and dynorphin, are more potent pain relievers when administered intraspinally than when injected intracranially [41].
Intake of a palatable sucrose solution modifies the actions of spiradoline, a kappa opioid receptor agonist, on analgesia and feeding behavior in male and female rats
2000, Pharmacology Biochemistry and Behavior