8-Phenyltheophylline reverses the antinociceptive action of morphine in the periaqueductal gray.
Morphine was injected into the periaqueductal gray region of the rat and 8-phenyltheophylline, an adenosine receptor antagonist, was injected intrathecally 15 or 30 min later, to determine whether supraspinally-administered morphine activated descending mechanisms to release adenosine (or a nucleotide which is metabolized to adenosine) from the spinal cord. 8-Phenyltheophylline (10 micrograms) reversed the antinociceptive action of morphine in the hot plate but not the tail-flick test. A combination of methysergide/phentolamine (15 micrograms each) reversed the action of morphine in both tests. 8-Phenyltheophylline retained the ability to reverse the action of morphine in the hot plate test in rats pretreated with 6-hydroxydopamine (to induce degeneration of descending noradrenergic pathways) but reversal was no longer observed in rats pretreated with 5,7-dihydroxytryptamine (after pretreatment with desipramine, to induce degeneration of descending serotonergic pathways). These results indicate that a component of the supraspinal antinociceptive action of morphine is due to release of adenosine or nucleotide, within the spinal cord and this release is dependent on intact serotonergic pathways.
Sawynok
J
J
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Espey
M J
MJ
Reid
A
A
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism; D000698:Analgesia; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013806:Theophylline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D015116:5,7-Dihydroxytryptamine; D009020:Morphine; D016627:Oxidopamine; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; D009638:Norepinephrine