Comparison of [(3)H]Glyburide binding with opiate analgesia, tolerance, and dependence in ICR and Swiss-Webster mice

Our laboratory demonstrated that morphine exhibits a modulatory control over the glyburide-binding site (sulfonylurea receptor) of the ATP-gated K(+) channel. This study evaluated the effect of chronic morphine administration on the sulfonylurea receptor during tolerance and physical dependence. ICR and Swiss-Webster mice were rendered tolerant to morphine by pellet implantation and were withdrawn by pellet removal. Alterations in the B(max) and K(D) were evaluated in mouse spinal cord using the radiolabeled ATP-gated K(+) channel blocker glyburide. The ED(50) for Swiss-Webster mice shifted from 13 to 451 mg/kg and thus they were more tolerant to morphine than ICR mice (ED(50) shift from 12 to 120 mg/kg). Swiss-Webster mice were also dependent to morphine only when the morphine pellet was in place, unlike ICR mice, which were dependent for 48 h after morphine pellet removal. Glyburide binding increased during chronic morphine treatment in Swiss-Webster mice by over 2-fold (from 294 to 635 fmol/mg of protein). This was not observed in ICR mice. In Swiss-Webster mice, chronic morphine treatment also significantly increased the K(D) by 3-fold (from 0.38 to 1.1 nM), whereas there was no change in affinity for ICR mice. Both strains of mice remained tolerant for 2 days after spontaneous withdrawal from morphine. However, the only increases in the B(max) and K(D) of glyburide were observed in Swiss-Webster mice that were highly tolerant to morphine. These results indicate that a high degree of tolerance is needed to alter ATP-gated potassium channels.