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.
Bibliographical noteFunding Information:
The helpful suggestions of D. (;. Lange are greatly appreciated. This study was supported bv National Institute on Drug Abuse Grant DA 00451 and a Veterans Administration Research Career Scientist Award to J. M. F.
- morphine-analgesic tolerance
- spinal/supraspinal multiplicity