Subsensitivity of serotonin and substance P receptors involved in nociception after repeated administration of a serotonin receptor agonist.
The antinociceptive effects of subcutaneous 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the responses to intrathecal (i.th.) serotonin (5-HT) and substance P (SP) were examined in mice after repeated administration of 5-MeODMT (3 mg/kg every 30 min for 4 hours). Ninety min after the last injection of 5-MeODMT the basal tail-flick and hot-plate response latencies were unaltered, but the antinociceptive effects of 5-MeODMT (3 mg/kg) in the tail-flick and hot-plate tests and the antinociceptive effect of 8-OH-DPAT (0.5 mg/kg) in the hot-plate test were markedly reduced. The behavioral responses to i.th. 5-HT (4.0 micrograms) and SP (2.5, 5, and 10 ng) which include vigorous biting, licking and scratching of the caudal part of the body, were attenuated 90-120 min after withdrawal of 5-MeODMT treatment. It is suggested that repeated administration of 5-MeODMT downregulates the function of the 5-HT receptors mediating the antinociceptive effects of 5-MeODMT and 8-OH-DPAT. The rapid desensitization to the behavioral responses both to 5-HT and SP by 5-MeODMT pretreatment may reflect a functional interaction between 5-HT and SP in the spinal modulation of nociception.
Eide
P K
PK
Department of Physiology, University of Bergen, Norway.
Hole
K
K
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology*; D051379:Mice; D009281:Naphthalenes / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000378:metabolism*; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014363:Tryptamines / Q000494:pharmacology*
D000700:Analgesics; D008732:Methoxydimethyltryptamines; D009281:Naphthalenes; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D014363:Tryptamines; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin