Stimulation of 5-HT1 receptors in the spinal cord changes substance P-induced behaviour.
This study examined whether intrathecal (i.th.) injection of different 5-hydroxytryptamine (5-HT) receptor agonists modulated the behavioural response to substance P. Given intrathecally, substance P produces a behavioural syndrome consisting of biting of the lower parts of the abdomen and reciprocal hindlimb scratching, which may be indicative of nociceptive stimulation. The number of substance P-induced bites was reduced when counted 5 min after intrathecal injection of 5-HT, p-chloroamphetamine (PCA) which causes release of 5-HT from neuronal terminals, the non-selective 5-HT receptor agonist quipazine, the selective 5-HT1 receptor agonists (+)-8-hydroxy-2-(di-n-propylamino)tetralin [(+)-8-OH-DPAT], 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (RU 24969) and 1(m-chlorophenyl)piperazine (mCPP), but was unchanged by treatment with the 5-HT2/5-HT1C receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). The number of scratches was significantly increased 5 min after injection of 5-HT and RU 24969. The results showed that intrathecal injection of 5-HT agonists, with a high affinity for the 5-HT1 receptor subtypes, reduced the total number of responses induced by intrathecal injection of substance P, whereas a 5-HT2/5-HT1C receptor agonist did not affect the behavioural response to the intrathecal injection of substance P.
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P K
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Department of Physiology, University of Bergen, Norway.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology; D000662:Amphetamines / Q000008:administration & dosage / Q000494:pharmacology; D000698:Analgesia; D000818:Animals; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009411:Nerve Endings / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D011814:Quipazine / Q000008:administration & dosage / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013239:Stereotyped Behavior / Q000187:drug effects*; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*
D000662:Amphetamines; D007211:Indoles; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; D013373:Substance P; D011814:Quipazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C015068:1-(3-chlorophenyl)piperazine