The relationship between morphine analgesia and the activity of bulbo-spinal serotonergic system as studied by tolerance phenomenon.
The effect of various doses of acute morphine on both analgesia and 5-hydroxytryptamine (5-HT) synthesis in the brain and the spinal cord has been studied in rats rendered tolerant by chronic administration of the analgesic. In morphine-tolerant rats, the incorporation of tritiated-L-tryptophan (TRP) in the brain and the spinal cord was higher than in non-tolerant rats, but there was no significant difference in the synthesis rate of the newly formed 5-HT between the two groups. An acute dose of morphine (10 mg/kg) which induced a powerful analgesia and a large increase in 5-HT synthesis in non-tolerant rats, did not produce analgesia nor changes in 5-HT synthesis in tolerant rats. Higher acute doses of morphine which restored analgesia in tolerant rats, induced a discrete increase in [3H]TRP incorporation and a marked increase in 5-HT synthesis in the spinal cord of these animals. The same doses significantly increased [3H]TRP incorporation in the forebrain but did not modify 5-HT synthesis. These results show that tolerance to morphine is associated with a decrease in the effects of the drug on 5-HT synthesis in the spinal cord and the brain and tend further support to the hypothesis that an enhancement of 5-HT synthesis in the spinal cord, induced independently of modifications of the availability of TRP, is associated with the analgesic effect of morphine.
D000818:Animals; D001933:Brain Stem / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects*; D011903:Raphe Nuclei / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D012684:Sensory Thresholds; D012701:Serotonin / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects*
D011957:Receptors, Opioid; D011985:Receptors, Serotonin; D012701:Serotonin; D009020:Morphine