Attenuation of opioid induced antinociception by 5-HT1A partial agonists in the rat.
The 5-HT1A partial agonists, buspirone, ipsapirone and gepirone did not affect the latency to respond in the tail flick test to heat. However, they strongly attenuated the antinociceptive action of the mu-opioids, morphine and sufentanil. The buspirone metabolite, 1-(2-pyrimidyl)pyridine (1-PP) was ineffective. BMY 7378, spiperone and alprenolol, putative antagonists at 5-HT1A sites, did not modify basal latencies or the action of morphine. TFMPP and mCPP, agonists at 5-HT1B and 5-HT1C sites, also did not affect basal latencies or morphine induced antinociception. These data show that 5-HT1A partial agonists attenuate morphine-evoked antinociception without affecting basal thresholds. They represent an interesting aspect of the interaction between opioids and serotonin in the control of nociception. In addition to opioids (Millan, 1986), serotonin (5-HT) is considered to play a major role in the control of pain and in the expression of opioid analgesia (Roberts, 1984). The identification of a multiplicity of binding sites for 5-HT in the CNS (Fozard, 1987) raises the question of their individual roles in nociceptive processes. The 5-HT1A site is of particular interest since it is present in high concentrations in the dorsal horn of the spinal cord (Daval, Verge, Basbaum, Bourgoin, and Hamon, 1987) and there are conflicting reports that it may mediate analgesia or hyperalgesia (Berge, Fasmer, Ogren, and Hole, 1985, Zemlan, Kow, and Pfaff, 1983). Indeed, the 5-HT1A agonist, 8-OH-DPAT, was reported to attenuate morphine-evoked antinociception in mice (Berge et al., 1985).(ABSTRACT TRUNCATED AT 250 WORDS)
Millan
M J
MJ
Neurobiology Division, FONDAX-Groupe de Recherche SERVIER, Puteaux, France.
Colpaert
F C
FC
D000526:Alprenolol / Q000494:pharmacology; D000700:Analgesics; D000818:Animals; D002065:Buspirone / Q000494:pharmacology; D005283:Fentanyl / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D011985:Receptors, Serotonin / Q000502:physiology*; D013134:Spiperone / Q000494:pharmacology; D017409:Sufentanil
D000700:Analgesics; D009294:Narcotics; D010879:Piperazines; D011743:Pyrimidines; D011985:Receptors, Serotonin; C018406:1-(3-trifluoromethylphenyl)piperazine; D013134:Spiperone; C043077:ipsapirone; D009020:Morphine; D000526:Alprenolol; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D017409:Sufentanil; C039979:gepirone; C053428:BMY 7378; D002065:Buspirone; D005283:Fentanyl