Differential ability of tachykinin NK-1 and NK-2 agonists to produce scratching and grooming behaviours in mice.
Potent and selective NK-1 and NK-2 agonists as well as compounds with lower selectivity and affinity for NK-1 binding sites were compared in their ability to produce scratching and grooming behaviours when injected intracerebroventricularly in mice. Septide, an agonist with a low affinity for NK-1 binding sites, [Sar9, Met(O2)11]SP and to a lesser extent [Pro9]SP, two potent and selective NK-1 agonists were the most effective drugs in stimulating these behaviours. Only high doses of [Apa9,10]SP and [Lys5, Tyr7, Pro8]NKA(4-10), two agonists with low affinity for NK-1 binding sites, produced scratching and grooming responses. Similarly, only high doses of [Lys5, MeLeu9, NLe10]NKA(4-10), a potent NK-2 agonist, produced grooming behaviour. When coinjected with the endopeptidase enzyme inhibitor phosphoramidon, the effects of [Apa9,10]SP, [Lys5, Tyr7, Pro8]NKA(4-10) and [Pro9]SP were markedly enhanced. Analyses of the potency of the different agents to displace 3H-SP binding in mouse subcortical structures revealed that the affinities of the agonists for NK-1 receptors are similar to those previously reported in rat brain. The efficacy of the agonists at producing behavioural responses was not equivalent to their potency to bind to central NK-1 receptors. These findings therefore suggest that a stimulation of NK-1 but also non classical NK-1 receptors are involved in the induction of scratching and grooming behaviours.
Ravard
S
S
Department of Psychopharmacology, Rhone Poulenc Rorer SA, CRVA, Vitry-sur-Seine, France.
Betschart
J
J
Fardin
V
V
Flamand
O
O
Blanchard
J C
JC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D006120:Grooming / Q000187:drug effects*; D008297:Male; D051379:Mice; D015288:Neurokinin A / Q000031:analogs & derivatives* / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000378:metabolism / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C083383:neurokinin A (4-10), Lys(5)-MeLeu(9)-Nle(10)-; C067285:substance P, Pro(9)-; C062618:substance P, Sar(9)-Met(O2)(11)-; D013373:Substance P; D015288:Neurokinin A