Establishment of Animal Models of Dementia with Neuropeptides and Development Study of Anti-Dementia Drugs

1. Galanin缩短了被动干扰学习的阶梯延迟，当多巴胺D-21-D2受体抑制剂SKF 38393，多巴胺D-22-D2受体抑制剂RU 24213，多巴胺D21型D2受体拮抗剂SCH 23390或多巴胺D22型D2受体拮抗剂S（-）-硫代失败以影响it. Dynorphin A-（1-13）SKF-38393，有意义地改进了加兰宁诱导的阶梯式延迟缩短。However，RU 24213，SCH 23390 or S（-）-sulpiride did not affect the galanin-induced shortening of step-down latency. δ伊D21 ye D2-and δ伊D22-selective opioid receptor agonists on spontaneous alternation performance， elevated plus-maze behavior and passive avoidance learning including step-down and step-through types were examined in mice。Although the δ D21-selective opioid receptor agonist， [D-Pen D12-selective opioid receptor agonist， L-Pen D15-D1] enkephalin （DPLPE） or the δ D22-selective opioid receptor agonist， [D-Ala-D12-selective opioid receptor agonist] delto ... More rphin II （deltorphin）并没有明显影响潜在的替代性能或提升的Plus Maze行为、DPLPE和deltorphin抑制的被动预防学习，包括阶梯式和阶梯式。D21-选择性阿片受体拮抗剂，7-苯并甲氧烷和D22-选择性阿片受体拮抗剂， naltriben，明显地拮抗了DPLPE和delta phin对被动抗干扰学习的抑制作用。在对比、DPLPE或德尔托芬没有被标记地影响行为反应在被动干扰学习培训期间通过电子休克诱导.目前的研究是为了澄清阿片类神经系统的负面影响，如Tachykinins NK D21 ye D2受体拮抗剂，物质P（SP），神经kinin NK D22 ye D2受体拮抗剂，神经kinin NK D22 ye D2受体拮抗剂，神经kinin A（NKA）。and the neurokinin NK，D23，D2受体抑制剂， senktide， on the scopolamine-induced impairment of spontaneous alternation performance in mice。SP、NKA和Senktide的Intracerebroventricular injections抑制了Scopolamine诱导的对固有替代性能的影响，而没有影响总的ARM条目，并指示Tachykinins的抗氨效应。Furthermore，SP的抑制作用，但不是NKA或Senktide的影响，几乎完全是通过预先处理纳洛酮来逆转的。However，SP对scopolamine诱导的对自发性替代性能的影响没有受到预处理对μ-opioid受体拮抗剂、β-funaltrexamine、δ-opioid受体拮抗剂、naltrindole和κ-opioid受体拮抗剂、正二元霉素的影响。Less（低）

1.Galanin shortened step-down latency of passive avoidance learning, while the dopamine DィイD21ィエD2 receptor agonist SKF38393, the dopamine DィイD22ィエD2 receptor agonist RU24213, the dopamine DィイD21ィエD2 receptor antagonist SCH23390 or the dopamine DィイD22ィエD2 receptor antagonist S(-)-sulpiride failed to influence it. Dynorphin A-(1-13) and SKF38393 markedly improved the galanin-induced shortening of step-down latency. However, RU24213, SCH23390 or S(-)-sulpiride did not affect the galanin-induced shortening of step-down latency.The effects of intracerebroventricular administration of δィイD21ィエD2- and δィイD22ィエD2-selective opioid receptor agonists on spontaneous alternation performance, elevated plus-maze behavior and passive avoidance learning including step-down and step-through types were examined in mice. Although the δィイD21ィエD2-selective opioid receptor agonist, [D-PenィイD12ィエD1, L-PenィイD15ィエD1] enkephalin (DPLPE) or the δィイD22ィエD2-selective opioid receptor agonist, [D-AlaィイD12ィエD1] delto … More rphin II (deltorphin) did not markedly affect spontaneous alternation performance or elevated plus-maze behavior, DPLPE and deltorphin inhibited passive avoidance learning including step-down and step-through types. The δィイD21ィエD2-selective opioid receptor antagonist, 7-benzylidenenaltrexone, and the δィイD22ィエD2-selective opioid receptor antagonist, naltriben, significantly antagonized the inhibitory effects of DPLPE and deltorphin on passive avoidance learning, respectively. In contrast, DPLPE or deltorphin did not markedly influence behavioral responses induced by electroshocks during training of passive avoidance learning.3.The present study was designed to clarify whether opioid neuronal systems are involved in the beneficial effects of tachykinins such as the neurokinin NKィイD21ィエD2 receptor agonist, substance P(SP), the neurokinin NKィイD22ィエD2 receptor agonist, neurokinin A(NKA), and the neurokinin NKィイD23ィエD2 receptor agonist, senktide, on the scopolamine-induced impairment of spontaneous alternation performance in mice. Intracerebroventricular injections of SP, NKA and senktide inhibited the scopolamine-induced impairment of spontaneous alternation performance without influencing total arm entries, indicating the antiamnesic effects of tachykinins. Furthermore, the inhibitory effects of SP, but not those of NKA or senktide, were almost completely reversed by pretreatment with naloxone. However, the effects of SP on the scopolamine-induced impairment of spontaneous alternation performance were not influenced by pretreatment with the μ-opioid receptor antagonist, β-funaltrexamine, the δ-opioid receptor antagonist, naltrindole, and the κ-opioid receptor antagonist, nor-binaltorphimine. Less