Development study of preventive and therapeutic drugs for Alzheimertype senile dementia by using biologically active peptides

1. P物质对东莨菪碱诱导的自发交替性能损伤的影响(1)P物质改善了东莨菪碱诱导的自发交替性能损伤。(2)速激肽NK-1受体拮抗剂WIN62577.2可拮抗P物质的改善作用。tyr - d - arg - ph - β - ala - nh_2 （TAPA）对被动回避学习的影响(1)TAPA对被动回避学习有抑制作用。(2)用mu-阿片受体拮抗剂-funaltrexamine治疗可以逆转TAPA的损伤作用。甘丙肽对被动回避学习、提升+迷宫学习和自发交替表现的影响(1)甘丙肽对被动回避学习有抑制作用，但对提升+迷宫学习和自发交替表现无影响。全身注射dynorphin A-(1-13)对环己亚胺所致被动回避学习障碍的影响(1)腹腔注射dynorphin A-(1-13)对环己亚胺所致被动回避学习障碍的影响。(2)卡帕-阿片受体拮抗剂-甲萘托非明可逆转dynorphin A-(1-13)的改善作用。δ -阿片受体激动剂对学习和记忆的影响(1)[D-Pen^2， L-Pen^5]脑啡肽和[D-Ala^2] δ啡肽II抑制被动回避学习，尽管它们不影响自发交替表现或提高+迷宫学习。这些结果表明，选择性阿片受体和δ阿片受体的阿片肽和丙氨酸可引起健忘症，而P物质和运动啡具有抗健忘症的作用。此外，它可能是一种促智神经肽。

1. Effects of substance P on scopolamine-induced impairment of spontaneous alternation performance(1) Substance P improved the scopolamine-induced impairment of spontaneous alternation performance.(2) The improving effects of substance P were antagonized by treatment with the tachykinin NK-1 receptor antagonist WIN62577.2. Effects of Tyr-D-Arg-Phe-beta-Ala-NH_2 (TAPA) on passive avoidance learning(1) TAPA inhibited passive avoidance learning.(2) The impairing effects of TAPA were reversed by treatment with mu-opioid receptor antagonist beta-funaltrexamine.3. Effects of galanin on passive avoidance learning, elevated plus-maze learning and spontaneous alternation performance(1) Galanin inhibited passive avoidance learning, although it had no effects on elevated plusmaze learning or spontaneous alternation performance.4. Effects of systemic administration of dynorphin A-(1-13) on cycloheximide-induced impairment of passive avoidance learning(1) The intraperitoneal injection of dynorphin A-(1-13) impaired the cycloheximide-induced impairment of passive avoidance learning.(2) The improving effects of dynorphin A-(1-13) were reversed by treatment with the kappa-opioid receptor antagonist nor-binaltorphimine.5. Effects of delta-opioid receptor agonists on learning and memory(1) [D-Pen^2, L-Pen^5] enkephalin and [D-Ala^2] deltorphin II inhibited passive avoidance learning, although they did not affect spontaneous alternation performance or elevated plus-maze learning.These results suggest that opioid peptides selective for mu-and delta-opioid receptors and galanin evoke anmesia, while substance P and dynorphin possess anti-amnesic effects. Moreover, it is possible that dynorphin is one of the nootropic neuropeptides.