Differential effects of forskolin and phorbol-13-myristate injected intrathecally or intracerebroventricularly on antinociception induced by morphine or beta-endorphin administered intracerebroventricularly in the mouse.
The effects of forskolin or phorbol-13-myristate (PMA) injected intrathecally (i.t.) or intracerebroventricularly (i.c.v.) on the inhibition of the tail-flick and hotplate responses induced by morphine or beta-endorphin administered i.c.v. were studied. Animals pretreated with forskolin (20 micrograms) i.t. for 10 min had an attenuated inhibition of the tail-flick response induced by i.c.v. administered morphine (2 micrograms) or beta-endorphin (1 microgram). However, i.t. pretreatment with PMA (100 ng) was not effective in reducing the inhibition of the tail-flick response induced by morphine or beta-endorphin administered i.c.v. In addition, i.t. pretreatment with either forskolin or PMA did not affect the inhibition of the hotplate response induced by morphine or beta-endorphin administered i.c.v. Forskolin pretreatment i.c.v. for 10 min attenuated the inhibition of the tail-flick and hotplate responses induced by i.c.v. administered morphine or beta-endorphin. However, i.c.v. pretreatment with PMA was not effective in reducing the inhibition of the tail-flick or hotplate responses induced by morphine or beta-endorphin administered i.c.v. Our results suggest that activation of adenylate cyclase located at both spinal and supraspinal sites appears to be involved in antagonizing antinociception induced by morphine and beta-endorphin administered supraspinally. However, spinal or supraspinal protein kinase C may not be involved in antagonizing antinociception induced by morphine or beta-endorphin administered supraspinally.
Suh
H W
HW
Department of Pharmacology, College of Medicine, Hallym University, Chunchon, Kangwon-Do, South Korea.
Song
D K
DK
Sim
Y B
YB
Chung
K M
KM
Kim
Y H
YH
D000262:Adenylyl Cyclases / Q000378:metabolism; D000698:Analgesia; D000818:Animals; D005576:Colforsin / Q000008:administration & dosage / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007700:Kinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage*; D010147:Pain Measurement; D011493:Protein Kinase C / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000494:pharmacology*; D001615:beta-Endorphin / Q000008:administration & dosage*
D005576:Colforsin; D001615:beta-Endorphin; D009020:Morphine; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate