Tachykinin NK(3)receptor involvement in anxiety.
This study investigates the effects of intracerebroventricular injection of selective agonists and antagonists of tachykinin NK(3)receptor on performance of mice in the elevated plus-maze test. Mice were treated with either vehicle or 1, 10, 100 or 500 pmol of neurokinin B or senktide ([succinil-Asp(6), MePhe(8)]substance P(6-11), a natural and synthetic selective NK(3)receptor agonists, respectively. Other mice received similar doses of [Trp(7)beta-Ala(8)]NKA(4-10)or SR 142801 ((S)-N-(1-(3-(1-benzoyl-3-(3, 4-dichlorophenyl)-piperidin-3-yl)propyl)-4-phenyl-piperidin- 4-yl)-N-m ethylacetamide) tachykinin NK(3)receptor selective peptide and non-peptide antagonists, respectively. Senktide significantly increased the frequency of entries and the time spent in the open arms, which is compatible with an anxiolytic action. Neurokinin B treatment did not alter the plus-maze parameters in a significant way. Conversely, the NK(3)peptide antagonist [Trp(7)beta-Ala(8)]NKA(4-10), but not SR142801 non-peptide antagonist, showed a reverse effect, i.e. an anxiogenic profile of action, reducing the frequency and the time spent in the open arms. Co-injection of either senktide plus [Trp(7)beta-Ala(8)]NKA((4-10)), or senktide plus SR 142801, blocked the effects promoted by senktide, indicating that centrally-administered NK(3)receptor agonists and antagonists can modulate experimental anxiety.
Ribeiro
S J
SJ
Department of Pharmacology, Universidade Federal de Santa Catarina, Rua Ferreira Lima, 82, Santa Catarina, 88015-420, Brazil.
Teixeira
R M
RM
Calixto
J B
JB
De Lima
T C
TC
D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D015288:Neurokinin A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D015287:Neurokinin B / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D015320:Tachykinins / Q000502:physiology*
D010446:Peptide Fragments; D010880:Piperidines; D018042:Receptors, Neurokinin-3; D015320:Tachykinins; C408447:neurokinin A (4-10), Trp(7)-beta-Ala(8)-; C054724:senktide; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B; C091554:SR 142801