Tachykinin NK3 receptor involvement in anxiety

This study investigates the effects of intracerebroventricular injection of selective agonists and antagonists of tachykinin NK3 receptor on performan ce of mice in the elevated plus-maze test. Mice were treated with either ve hicle or 1, 10, 100 or 500 pmol of neurokinin B or senktide ([succinil-Asp( 6), MePhe(8)]substance P6-11, a natural and synthetic selective NK3 recepto r agonists, respectively. Other mice received similar doses of [Trp(7)beta- Ala(8)]NKA(4-10) or SR142801 ((S)-N-(1-(3-(1-benzoyl-3-(3,4-dichrorophenyl) -piperidin-3-yl)propyl)-4-phenyl-piperidin-4-yl)-N-methylacetamide) tachyki nin NK3 receptor selective peptide and non-peptide antagonists, respectivel y. Senktide significantly increased the frequency of entries and the time s pent in the open arms, which is compatible with an anxiolytic action. Neuro kinin B treatment did not alter the plus-maze parameters in a significant w ay. Conversely, the NK3 peptide antagonist [Trp(7)beta-Ala(8)]NKA(4-10), bu t not SR142801 non-peptide antagonist, showed a reverse effect, i.e. an anx iogenic 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 SR142801, blocked the effects promoted by senktide, indicating that centrally-administered NK3 receptor agonists and antagonist s can modulate experimental anxiety.