Effect of prolonged administration of clonidine on [3H]PN 200-110 and [125I]omega-conotoxin binding in mouse brain.

The effect of chronic exposure to clonidine or morphine on clonidine- and morphine-induced analgesia in mice was examined. Binding of L- or N-type calcium channel antagonist to cortical membrane fractions was also compared between these groups of mice. A decrease in the analgesic effect of clonidine and morphine was observed following prolonged administration of clonidine or morphine. Binding of [3H]PN 200-110, an L-type calcium channel antagonist, decreased following prolonged administration of clonidine whereas it increased after morphine treatment. On the other hand, a significant increase of [125I]omega-conotoxin, an N-type calcium channel antagonist, binding was observed after chronic clonidine or morphine treatment. These results will be discussed in relation with the possible development of cross-tolerance between clonidine and morphine through the change in calcium channels, more specifically in N-type channels.