Evaluation of the direct actions of drugs with a serotonergic link in spinal analgesia on the release of [3H]serotonin from spinal cord synaptosomes.
Morphine, ketamine, ethylketocyclazocine and quipazine, drugs with an apparent local spinal serotonergic action, which contributes to their analgesic effects, were tested for their ability to alter the release of [3H]serotonin ([3H]5-HT) from a synaptosomal preparation from the spinal cord of the rat. Related compounds including [D-Ala2, D-Leu5]enkephalin (DADLE), n-allylnormetazocine and phencyclidine were also examined. None of the drugs was found to be capable of inducing a direct release of [3H]5-HT or of facilitating potassium-induced release of 5-HT. However, quipazine inhibited the depressant action of exogenous 5-HT on overflow of 3H (mediated through the 5-HT autoreceptor), an action that should facilitate serotonergic neurotransmission. In contrast to the other drugs, DADLE was found to depress K+ stimulated release of 5-HT. The results suggests that the serotonergic mechanism involved in the antinociceptive action of some of these drugs (i.e. ketamine, morphine and ethyl-ketocyclazocine) is not related to direct presynaptic interactions to promote release of 5-HT. On the other hand, a small population of serotonergic nerves critical for analgesia may be involved and are not detected using tissue from the whole spinal cord, However, it seems equally plausible that these drugs may produce their antinociceptive action through interactions with other neurotransmitter systems that in turn interface with the serotonergic nerves, perhaps through interneurons or collateral connections.
D000698:Analgesia; D000818:Animals; D002118:Calcium / Q000502:physiology; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D016314:Ethylketocyclazocine; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*
D011985:Receptors, Serotonin; D012701:Serotonin; D011814:Quipazine; D016314:Ethylketocyclazocine; D007649:Ketamine; D009020:Morphine; D003496:Cyclazocine; D011188:Potassium; D002118:Calcium