Morphine-induced analgesia potentiated by a 5-HT1A anxiolytic, tandospirone, in spontaneously hypertensive rats

We examined a 5-HT 1A antianxiety compound, tandospirone, with respect to its analgesic properties in morphine-induced analgesia using Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In the foot-shock vocalization and the thermal tail-flick latency tests, single-day and/or ten consecutive days of administration of tandospirone in SHR enhanced morphine-induced analgesia, although the addition of tandospirone did not augment opioid analgesia in WKY. We also investigated the properties of tandospirone and its main metabolite with respect to brain opioid receptors in SHR. Displacement of in vitro binding at mu and kappa opioid receptors by tandospirone indicated a modest affinity of the drug for kappa (IC 50 = 5.7 μM) and mu (IC 50 = 18.4 μM) with a Hill slope which approximated 1, although the primary metabolite of tandospirone, 1-pyrimidinyl-piperazine-dihydrochloride, did not bind to kappa sites and had a very low affinity to mu sites. At delta opioid receptors, displacement by both the parent compound and the metabolite was weak, with a similar affinity. In conclusion, we postulate that tandospirone has a weak affinity for brain kappa and mu opioid receptors, and that co-administration of tandospirone and morphine causes a potentiation of analgesia in SHR