SITES OF ACTION OF NALOXONE IN PRECIPITATING WITHDRAWAL JUMPING IN MORPHINE-DEPENDENT MICE - INVESTIGATIONS BY THE ED(50) VALUE AND CNS CONTENT OF NALOXONE
Y. Miyamoto et Ae. Takemori, SITES OF ACTION OF NALOXONE IN PRECIPITATING WITHDRAWAL JUMPING IN MORPHINE-DEPENDENT MICE - INVESTIGATIONS BY THE ED(50) VALUE AND CNS CONTENT OF NALOXONE, Drug and alcohol dependence, 32(2), 1993, pp. 163-167
The sites of action of naloxone and the possible interaction between s
upraspinally and spinally administered naloxone in precipitating withd
rawal jumping were investigated by comparing the ED50 value and centra
l nervous system (CNS) content of naloxone after three different admin
istration routes in morphine-dependent mice. ED50 values of naloxone f
or i.c.v., i.t. and s.c. routes were 18.8 nmol, 1.95 nmol and 50.6 nmo
l/kg, respectively. Jumping occurred most often within 5 min after i.t
administered naloxone, but it took more than 10 min to reach the most
frequent jumping after s.c. and i.c.v. administered naloxone. After e
qui-effective doses (ED50) of naloxone were administered i.c.v., i.t.
or s.c., the content of naloxone in the brain was 70 times lower after
s.c. than that after i.c.v. injection. The concentration of naloxone
in the spinal cord was 37 times lower after s.c. than that after i.t.
injection. The ED50 values of naloxone and the time courses of jumping
suggest that spinal sites appear to be more important than the supras
pinal sites and comparisons of naloxone-content suggest that there is
a synergistic interaction between supraspinal- and spinal-naloxone aft
er systemic administration.