Is tolerance to intrathecal morphine in intact rats supraspinally mediated?

The effect of repeated intrathecal (IT) injections of 5 micrograms of morphine on the tail flick (TF) was determined in rats that were tested either 0.5 h or 5.0 h after administration on each of five successive days. Tolerance developed rapidly in animals tested 5.0 h after each injection. Animals tested 0.5 h after each injection did not become tolerant. Animals that were tested 5.0 h after an intrathecal saline injection on the first four days were also tolerant to a 5 micrograms dose of morphine on the fifth day. These data are discussed in the context of previous conflicting reports concerning tolerance to intrathecal morphine. It is suggested that, under certain conditions, tolerance to intermittent intrathecal morphine administration may be due to a supraspinal opiate action.