Involvement of supraspinal and spinal
mu opioid receptors in the development degree of
morphine dependence was estimated by the ED50 values of
naloxone (s.c.) required to precipitate withdrawal jumping and
diarrhea 72 hr after
morphine-pellet implantation.
beta-FNA was administered 4 times (24 hr before, just before, 24 and 48 hr after
morphine-pellet implantation) by the i.c.v. or i.t. route.
beta-FNA (both i.c.v. and i.t. routes) significantly increased the ED50 values of
naloxone for jumping and
diarrhea and the increase in the ED50 value of
naloxone for jumping was much greater than that for
diarrhea. I.c.v. administered
beta-FNA was more potent in increasing the ED50 value of
naloxone for jumping than i.t. administered
beta-FNA. On the other hand, i.c.v. administered
beta-FNA was equipotent with i.t. administered
beta-FNA in increasing the ED50 value of
naloxone for
diarrhea. These results suggest that both supraspinal and spinal
mu opioid receptors are involved in the development of
morphine dependence and that supraspinal
mu receptors play a more important role than spinal
mu receptors in withdrawal jumping which may reflect an excitation of the central nervous system whereas supraspinal and spinal
mu receptors have similar importance in withdrawal
diarrhea which may reflect an abnormal function of the autonomic nervous system.