Roerig S C, O'Brien S M, Fujimoto J M, Wilcox G L
Brain Res. 1984 Aug 13;308(2):360-3. doi: 10.1016/0006-8993(84)91078-3.
Mice injected with morphine at both a supraspinal (intracerebroventricular) and a spinal (intrathecal) site showed a multiplicative interaction between sites for the tail-flick analgesic response. In morphine pellet-implanted mice, the decrease in this interaction was the source of tolerance developed to subcutaneous morphine whereas the separate sites showed no tolerance. During morphine withdrawal (after removal of the morphine pellet) synergism between sites returned but the separate sites showed development of tolerance.
