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

1.Galanin shortened step-down latency of passive avoidance learning，while the dopamine D - 21 D2 receptor agonist SKF38393the dopamine D - 22 D2 receptor agonist RU24213，the dopamine D - 21 D - 2 receptor antagonist SCH23390 or the dopamine D - 22 D - 2 receptor antagonistS(-)-sulpiride failed to influence it. Dynorphin A-(1-13) and SKF38393 markedly improved thegalanin-induced shortening of step-down latency. However, RU24213，SCH23390 or S(-)-sulpiride did not affect the galanin-induced shortening of step-down latency.Theeffects of intracerebroventricular administration of δ D21 D2- and δ D22 D2-selective opioidreceptor agonists on spontaneous alternation performance，elevated plus-maze behavior and passive avoidance learning including step-down and step-throughtypes were examined in mice. Although the δ d -selective opioid receptor agonist，[D-Pen - D12 - D1，L-Pen - D15 - D1] enkephalin (DPLPE) or the δ - D22 -selective opioid receptor agonist，[D-Ala] delto…rphin II （deltorphin）不明确影响spontaneous alternation performance orelevated plus-maze behaviorDPLPE和deltorphin inhibited passive avoidance learning including step-down and step-throughtypes. The δ d -selective opioid receptor antagonist, 7-benzylidenenaltrexone，D22 -selective opioid receptor antagonist, naltriben，significantly antagonized the inhibitory effects of DPLPE and deltorphin on passive avoidancelearning, respectively. In contrast，DPLPE or deltorphin did not markedly influence behavioral responses induced by electroshocks duringtraining of passive avoidance learning.3.The present study was designed to clarify whether opioidneuronal systems are involved in the beneficial effects of tachykinins such as the neurokininNK - D21 - D2 receptor agonist, substance P(SP), the neurokinin NK - D22 - D2 receptor agonist，neurokinin A(NKA), and the neurokinin NK D23 - 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 performancewithout influencing total arm实体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 werenot influenced by pretreatment with the μ-opioid receptor antagonist, β-funaltrexaminethe δ-opioid receptor antagonist, naltrindole, and the κ-opioid receptor antagonist，nor-binaltorphimine . less

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