Serotonin receptor antagonists induce hyperalgesia without preventing morphine antinociception.
5-Hydroxytryptamine (5-HT) receptor blockade by administration of mianserin (1 mg/kg) or metergoline (0.25 mg/kg) shortened the response latencies of rats in the hot-plate (hind-paw lick response) and tail-flick tests, but did not consistently attenuate the antinociceptive effect of morphine (1.25--5.0 mg/kg). Injection of the opiate receptor antagonist naloxone (1 mg/kg) did not change tail-flick response latencies and did not interfere with the antinociceptive action of the 5-HT receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). The antinociceptive effect of morphine was reduced in chronically spinal rats, although significant increases in tail-flick latencies were observed after 2.5 and 5.0 mg/kg. Concomitant administration of 5-MeODMT failed to restore the effect of morphine in spinal rats. In the hot-plate test, morphine did not reliably prolong latencies to forepaw lick, indicating that this response is not a useful measure of pain sensitivity. The results suggest that different mechanisms underlie the analgesia induced by systemic administration of morphine and 5-HT mediated tonic inhibition of nociception.
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D008803:Mianserin / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology
D000700:Analgesics; D011985:Receptors, Serotonin; D008711:Metergoline; D008803:Mianserin; D009270:Naloxone; D009020:Morphine