The effect of opioid agonists and antagonists on gastrointestinal motility in mice selected for high and low swim stress-induced analgesia.
BACKGROUND
The opioid system in the gastrointestinal (GI) tract plays an important physiological role, but is also responsible for the side effect of opioid drugs, including troublesome constipation in chronic pain treatment. The aim of this study was to characterize and validate a new mouse model to study the effects of opioid agonists and antagonists in the GI tract.


METHODS
Six-week-old male Swiss-Webster mice, divergently bred for high (HA) and low (LA) swim stress-induced analgesia (SSIA), were used in the study. To assess the influence of opioid agonists (morphine and loperamide) and antagonists (naloxone hydrochloride, NLX and naloxone methiodide, NLXM) on GI motility, whole GI transit (whole GIT) and upper GIT assays were conducted. To evaluate the expression of opioid receptors in the ileum and colon of HA and LA mice, immune staining was performed.


RESULTS
The effect of morphine was more pronounced in HA line, whereas loperamide exerted a stronger effect in LA mice. Furthermore, NLX and NLXM differentially abolished the inhibitory action of the central and peripheral opioid system on whole and upper GIT in HA and LA mice. The differences in GI motility between HA and LA mice coexisted with parallel changes in the expression of opioid receptors in the ileum and colon.


CONCLUSIONS
Differences in the activity of the endogenous opioid system are responsible for the vulnerability to changes in GI motility during treatment with opioids. Our findings validate the HA/LA model for further studies on opioids in the GI tract.
Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
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Wasilewski
Department of Neuropeptide Laboratory, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.|Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
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A
Lesniak
Department of Pharmacodynamics, Centre for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, Poland.
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Bujalska-Zadrozny
Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Magdalenka, Poland.
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B
Sadowski
Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
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J
Fichna
Department of Neuropeptide Laboratory, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.|Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Magdalenka, Poland.
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Sacharczuk
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009292:Narcotic Antagonists / Q000494:pharmacology; D013315:Stress, Psychological
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists
gastrointestinal transit; opioid system activity; selected mouse lines; swim stress-induced analgesia