Potentiation of opiate analgesia and apparent reversal of morphine tolerance by proglumide

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Science  27 Apr 1984:
Vol. 224, Issue 4647, pp. 395-396
DOI: 10.1126/science.6546809


Exogenous cholecystokinin selectively antagonizes opiate analgesia, which suggests that endogenous cholecystokinin may act physiologically as an opiate antagonist and may play a role in opiate tolerance. The use of the selective cholecystokinin antagonist proglumide provided a test of these hypotheses in rats that were either inexperienced with or tolerant to opiates. Proglumide potentiated analgesia produced by morphine and endogenous opiates and seemed to reverse tolerance. These results suggest that endogenous cholecystokinin systems oppose the action of opiates.