Behavioural NeuroscienceResearch PaperDifferential noxious and motor tolerance of chronic delta opioid receptor agonists in rodents
Section snippets
Studies in rats
Adult male Sprague–Dawley rats (200–225 g; Charles-River, St-Constant, QC, Canada) were maintained on a 12-h light/dark cycle (6:00–18:00 h). Laboratory chow and water were available ad libitum. Studies were conducted between 7:00 and 11:00 (light cycle). Experiments were approved by the animal care committee of the Université de Sherbrooke in compliance with the policies and directives of the Canadian Council on Animal Care and guidelines from the International Association for the Study of
Unilateral inflammation: visual confirmation
Injection of CFA into the plantar surface of the right hind paw rapidly induced edema and swelling that persisted over at least 3 days (72 h), after which both rats and mice avoided bearing their body weight on their inflamed hind paw.
Experiments performed in rats.
Antihyperalgesic potency of intrathecal deltorphin II and morphine
As shown in Fig. 1A, intrathecal injection of deltorphin II induced a time- and dose-dependent alleviation of CFA-induced ipsilateral thermal hyperalgesia. For all effective doses of deltorphin II, the effect was maximal at 15 min
Discussion
In the present study, we investigated the effects of multiple injections of DOPR-selective agonists (deltorphin II and SB-235863) using various treatment and assessment paradigms. In a model of CFA-induced inflammation, we found a lack of both acute and chronic tolerance to delta agonists' antihyperalgesic effect. By contrast, when DOPR-mediated motor incoordination/ataxia-like and antinociception (acute pain) behaviors were assessed, repeated injection of deltorphin II was found to reduce
Conclusion
In conclusion, the present study proves the existence of a dichotomy between development of tolerance regarding diverse behavioral effects mediated by DOPR activation. In particular, we demonstrated a lack of antihyperalgesic tolerance to delta-selective agonists in a model of peripheral inflammation induced by injection of CFA into the plantar surface of the paw. As opposed to its antihyperalgesic effect, development of tolerance to deltorphin II was observed when its antinociceptive
Acknowledgments
We thank Nicolas Beaudet for his critical reading of the manuscript. This work was supported by grants MOP-84538 from the Canadian Institutes of Health Research (CIHR) to L.G. and DA11672 from the National Institutes of Health (NIH) to C.C. H.B. was the recipient of a scholarship from the Alexander Graham Bell Canada Graduate Scholarships Program awarded by the Natural Sciences and Engineering Research Council of Canada (NSERC).
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