Proglumide prevents and curtails acute tolerance to morphine in rats

The antagonism of the antinociceptive action of morphine elicited by CCK-8-SO4 can be counteracted by proglumide, a CCK antagonist. The addition of morphine (10(-6)M) to the artificial spinal fluid perfusing the subarachnoidal space of rat spinal cord increases the CCK content of the perfusate. Proglumide can potentiate morphine analgesia without changing the half life of morphine. After seven to eight subcutaneous injections of morphine (4 mg/kg) repeated every two hrs there is tolerance to the antinociceptive action of morphine. Proglumide can partially block or reverse this acute tolerance to morphine.