Potentiation of a behavioural response in mice by spinal coadministration of substance P and excitatory amino acid agonists.

Article date: 1991/11/25

PubMed ID: 1724310

Journal name: Neuroscience letters (ISSN: 0304-3940)


The functional interaction in the spinal cord between substance P and excitatory amino acid agonists was investigated. Behavioural responses were scored in mice after intrathecal administration of excitatory amino acid agonists and substance P, given separately or in combination. A strong potentiation of the effect was seen when substance P was coadministered with N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) or kainic acid (KA). The potentiation was blocked by the corresponding antagonists: the selective NMDA-receptor antagonist (+/-)-3- (2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the substance P analog, [D-Arg1,D-Trp7,9,Leu11]-substance P (Spantide). These findings indicate a functional interaction between substance P and glutamate in the dorsal horn of the spinal cord, compatible with the hypothesis that corelease of substance P and glutamate from primary afferent neurons may enhance nociception.

Author List: Mjellem-Joly N, Lund A, Berge O G, Hole K

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Amino Acids; Analgesics; Piperazines; Quinoxalines; Receptors, N-Methyl-D-Aspartate; Ibotenic Acid; Substance P; N-Methylaspartate; 6-Cyano-7-nitroquinoxaline-2,3-dione; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; spantide; 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; Kainic Acid;

Mesh terms: 6-Cyano-7-nitroquinoxaline-2,3-dione; Amino Acids/physiology; Analgesics/pharmacology; Animals; Behavior, Animal/drug effects; Drug Synergism; Ibotenic Acid/analogs & derivatives; Injections, Spinal; Kainic Acid/antagonists & inhibitors; Male; Mice; Mice, Inbred Strains; N-Methylaspartate/antagonists & inhibitors; Nociceptors/drug effects; Piperazines/pharmacology; Quinoxalines/pharmacology; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors; Substance P/administration & dosage; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

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