CCK Modulates Morphine Induced Analgesia on the Rat Paw Pressure Test via the Central CCK-B Receptors.

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The effects of cholecystokinin octapeptide (CCK-8) and its selective antagonists (proglumide, MK-329) on morphine induced analgesia (MIA) in the paw pressure test of the Wistar-SPF male rats were investigated. Baseline pain thresholds indicated that the morning (09:00-12:00) testing were significantly higher than the afternoon (14:00-18:00) testing. This result supports that diurnal variation of endogenous opioids. MIA was shown clear (p<0.01) dose-dependent (1.5-15mg/kg, i. p., n=6) manner with significant correlation coefficient (y=3.98x+22.67, r=0.827, p<0.001). CCK significantly (p<0.01) reduced MIA. Both proglumide (5-50mg/kg) and MK-329 (0.5-5.0mg/kg) were enhanced MIA. Especially, MK-329 has shown potently enhanced MIA. i. e. it showed desinhibition to the CCK's inhibitory action to MIA. These results suggest that CCK play important role to the endogenous opioids antagonist via through CCK-B receptors and to the function of the pain/analgesic mechanisms.
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