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

1. P物质对东莨菪碱引起的自发交替操作损伤的影响（1）P物质改善东莨菪碱引起的自发交替操作损伤。(2)用速激肽NK-1受体拮抗剂WIN62577.2可拮抗P物质的改善作用。Tyr-D-Arg-Phe-beta-Ala-NH_2（TAPA）对被动回避学习的影响（1）TAPA抑制被动回避学习。(2)μ-阿片受体拮抗剂β-funalcumamine可逆转TAPA的损伤作用。甘丙肽对大鼠被动回避学习、高架十字迷宫学习和自发交替行为的影响（1）甘丙肽抑制大鼠被动回避学习，但对高架十字迷宫学习和自发交替行为无影响.强啡肽A-（1-13）对环己酰亚胺所致被动回避学习障碍的影响（1）腹腔注射强啡肽A-（1-13）可减轻环己酰亚胺所致的被动回避学习障碍。(2)强啡肽A-（1-13）的改善作用可被κ-阿片受体拮抗剂去甲binaltorphimine逆转。δ-阿片受体激动剂对学习记忆的影响（1）[D-Pen^2，L-Pen^5]脑啡肽和[D-Ala^2] deltorphin II抑制被动回避学习，但不影响自发交替行为或增强的十字迷宫学习。这些结果表明，选择性μ-和δ-阿片受体的阿片肽和甘丙肽引起失忆，而P物质和强啡肽具有抗遗忘作用。强啡肽可能是促智性神经肽之一。

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.