Multiplicative interaction between intrathecally and intracerebroventricularly administered morphine for antinociception in the mouse: effects of spinally and supraspinally injected 3-isobutyl-1-methylxanthine, cholera toxin, and pertussis toxin.
1. Either intrathecal (i.t.) or intracerebroventricular (i.c.v.) administration of morphine alone at the dose of 0.2 microgram slightly increased inhibition of the tail-flick response. However, combined i.t. and i.c.v. injections of morphine at the same dose increased the inhibition of the tail-flick response in a synergistic manner. 2. Cholera toxin (CTX, 0.05 to 0.5 microgram) pretreated i.t. or i.c.v. for 24 hr or pertussis toxin (PTX, 0.05 to 0.5 microgram) for 6 days dose-dependently attenuated inhibition of the tail-flick response induced by combined i.t. and i.c.v. injection of morphine. 3. 3-Isobutyl-1-methylxanthine (IBMX, 0.001 to 0.1 ng) pretreated i.t. for 10 min dose-dependently attenuated the inhibition of the tail-flick response induced by combined i.t. and i.c.v. injections of morphine. However, IBMX pretreated i.c.v. for 10 min was not effective in attenuating the inhibition of the tail-flick response induced by combined i.t. and i.c.v. injections of morphine. 4. It is concluded that both spinal and supraspinal CTX- and PTX-sensitive G-proteins are involved in the antinociception produced by morphine-induced multiplicative interaction between spinal and supraspinal sites. However, only spinal but not supraspinal cAMP phosphodiesterase is involved in mediating antinociception induced by morphine-induced multiplicative interaction.
Suh
H W
HW
Department of Pharmacology and Institute of Natural Medicine, Hallym University, Chunchon, Kangwon-Do, S. Korea.
Sim
Y B
YB
Choi
Y S
YS
Song
D K
DK
Kim
Y H
YH
D015056:1-Methyl-3-isobutylxanthine / Q000008:administration & dosage / Q000494:pharmacology*; D000698:Analgesia; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002772:Cholera Toxin / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000008:administration & dosage / Q000494:pharmacology*
D000701:Analgesics, Opioid; D010566:Virulence Factors, Bordetella; D009020:Morphine; D002772:Cholera Toxin; D037342:Pertussis Toxin; D015056:1-Methyl-3-isobutylxanthine