Marco N, Thirion A, Mons G, Bougault I, Le Fur G, Soubrié P, Steinberg R
Sanofi Recherche - Neuropsychiatry Department, Montpellier, France.
Neuropeptides. 1998 Oct;32(5):481-8. doi: 10.1016/s0143-4179(98)90075-0.
The regulation of dopaminergic and cholinergic function by neurokinin-3 (NK3) receptor activation was examined in vivo in urethane-anaesthetized guinea pigs with microdialysis probes. The local application of the NK3 tachykinin receptor agonist senktide in the region of dopamine cell bodies (pars compacta of the substantia nigra and ventral tegmental area) and in the area of cholinergic cell bodies (septal area) markedly enhanced the extracellular dopamine (DA) and acetylcholine (ACh) concentration throughout their respective target areas, i.e. striatum, nucleus accumbens, prefrontal cortex for dopaminergic systems and hippocampus for cholinergic neurons. The enhancing effect of senktide on neurotransmitter release was dose dependently blocked by the selective non-peptide NK3 receptor antagonist SR142801 (0.1-1 mg/kg, i.p.), whereas its inactive S-enantiomer SR142806 (0.3-1 mg/kg, i.p.) did not exert any antagonistic activity on the effect of intranigral or intraseptal application of senktide. These results demonstrate that NK3 receptors can modulate the activity of central DA and ACh systems.
采用微透析探针，在氨基甲酸乙酯麻醉的豚鼠体内研究了神经激肽-3（NK3）受体激活对多巴胺能和胆碱能功能的调节作用。在多巴胺细胞体区域（黑质致密部和腹侧被盖区）以及胆碱能细胞体区域（隔区）局部应用NK3速激肽受体激动剂senktide，可显著提高其各自靶区域（即多巴胺能系统的纹状体、伏隔核、前额叶皮质以及胆碱能神经元的海马体）的细胞外多巴胺（DA）和乙酰胆碱（ACh）浓度。选择性非肽类NK3受体拮抗剂SR142801（0.1 - 1 mg/kg，腹腔注射）可剂量依赖性地阻断senktide对神经递质释放的增强作用，而其无活性的S-对映体SR142806（0.3 - 1 mg/kg，腹腔注射）对黑质内或隔区内应用senktide的效果没有任何拮抗活性。这些结果表明，NK3受体可调节中枢DA和ACh系统的活性。
