Effects of various serotoninergic agonists and an antagonist on a nociceptive reaction in mice

Low doses of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), quipazine and cyproheptadine produced facilitation of jumping in mice using the hot plate method. Higher doses produced severe motor disturbances which precluded the assessment of effects on nociception. The observed hyperalgesia might be a consequence of diminution of serotoninergic tone resulting either from triggering of presynaptic serotoninergic receptors in the case of 5-MeODMT and quipazine or from the blockade of postsynaptic serotoninergic receptors in the case of cyproheptadine. The 5-MeODMT-induced hyperalgesia was not attenuated by buprenorphine, which under similar conditions antagonized completely the hyperalgesic effects of naloxone; thus, the hyperalgesic effects of 5-MeODMT do not seemingly involve opioidergic receptors.