Comparative behavioural profile of centrally administered tachykinin NK1, NK2 and NK3 receptor agonists in the guinea-pig.
1. The NK1 tachykinin receptor agonists, septide, [Sar9,Met(O2)11]SP and [Pro9]SP produced locomotor hyperactivity (10-20 min) when injected intracerebroventricularly (i.c.v.) in the guinea-pig. The most potent in eliciting this hyperactivity was septide (from 0.63 to 5 micrograms), compared to [Sar9,Met(O2)11]SP, which was active at 2.5 and 5 micrograms and [Pro9]SP which induced a non-significant increase even at 10 micrograms. 2. Wet-dog shakes were elicited by septide, [Sar9,Met(O2)11]SP and [Pro9]SP injected by the i.c.v. route in the guinea-pig. [Sar9,Met(O2)11]SP, active from 0.16 to 2.5 micrograms was more potent than septide (active at 1.25 micrograms) and [Pro9]SP (active at 0.63 micrograms) in eliciting such behaviour. To a lesser extent, grooming was also observed after injection of these agonists. 3. The NK2 tachykinin receptor agonist, [Lys5,MeLeu9,Nle10]NKA(4-10), up to the dose of 10 micrograms i.c.v. had no effect in the guinea-pig. It neither modified locomotor activity nor induced a characteristic behavioural response. At higher doses (20 micrograms), some toxic effects were noted. 4. The NK3 tachykinin receptor agonist, senktide, contrasts with the NK1 receptor agonists in that it elicited only wet-dog shakes, at doses ranging from 0.32 to 1.25 micrograms. It neither modified locomotor activity (1 microgram) nor induced grooming (up to 5 micrograms) in the guinea-pig. 5. To our knowledge, these results are the first demonstration that the guinea-pig could be useful to differentiate tachykinin agonists on the basis of their behavioural profile, distinct from those obtained in mice and rats.
Piot
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Rhone-Poulene Rorer S.A., Centre de Recherche de Vitry-Alfortville, Vitry sur Seine, France.
Betschart
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Grall
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I
Ravard
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S
Garret
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Blanchard
J C
JC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D006168:Guinea Pigs; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D015288:Neurokinin A / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D018040:Receptors, Neurokinin-1 / Q000819:agonists*; D018041:Receptors, Neurokinin-2 / Q000819:agonists*; D018042:Receptors, Neurokinin-3 / Q000819:agonists*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology
D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; C067285:substance P, Pro(9)-; C062618:substance P, Sar(9)-Met(O2)(11)-; D013373:Substance P; C054725:septide; D015288:Neurokinin A; C056408:neurokinin A(4-10); D011761:Pyrrolidonecarboxylic Acid