mGluR2R ( IC50 = 5 nM ); mGluR3R ( IC50 = 24 nM )

LY-354740 下调斑点 1014、1822（缺氧上调蛋白 1）、4513（蛋白二硫键异构酶 3 的亚型）、6204、6312、7306（26S 蛋白酶体非 ATP 酶调节亚基 7）以及蛋白斑点 1013 和6005（结蛋白），并上调小鼠皮质神经元中的点 6507（塌陷素反应介导蛋白 1）[2]。

LY-354740（15 或 30 mg/kg，ip）对 Gria1−/− 或 WT 小鼠的空间工作记忆表现没有影响，并且对 Gria1−/ 中短试验间隔的奖励交替测试没有影响- 和浓度为 30 mg/kg 的 WT 小鼠。 LY354740（15 或 30 mg/kg，腹腔注射）可降低野生型和 Gria1−/− 小鼠的自发运动活动[1]。 LY354740（15 mg/kg，腹膜内注射）可在首次接触的 GluA1-KO 和预处理的 GluA1-KO 雄性中引起新奇诱导的过度运动，但在雌性中则不然。 LY354740（15 mg/kg，腹腔注射）显着降低 GluA1-KO 雄性的 c-Fos 表达增加至 WT 雄性的水平，但不降低雌性的水平[3]。 LY354740（10 mg/kg，腹腔注射）可减弱固定应激诱导的大鼠 mPFC 中 BDNF mRNA 表达的增加[4]。

Mice: Experiment 1A involves 30 drug-free testing trials (five trials per day for six days) for wild-type (female: N = 6; male: N = 5) and Gria1^−/− (female: N = 7; male: N = 8) mice. Each animal is then tested on rewarded alternation following an injection of either Eglumegad (LY354740) (15 mg/kg) or vehicle. Animals are given injections, and then they are kept in their home cage for 30 minutes before behavioral testing starts. In the T-maze, ten trials of rewarded alternation are given to each animal. Mice are allowed a maximum of 120 seconds to finish a trial. The animals are retested without receiving any medication at least 24 hours after the initial round of drug testing to make sure the drug has no long-term effects and the mice continue to perform at a high level during alternation. After retesting for twenty-four hours, mice are given ten more trials of rewarded alternation testing, but this time they are administered a drug that they have not previously received. Considering the quantity of mice, every effort is made to counterbalance the order of drug exposure within genotype and sex. All trials in which the animal alternated are counted, along with the amount of time it took to run (sample latency) from the start arm to the food well and the amount of time it took to make a decision (choice latency) during the choice run. Utilizing a stopwatch, the researcher determines latencies. For the duration of the experiment, the researcher is blind to the animals' genotype and drug allocations. A higher dose of Eglumegad (LY354740) (30 mg/kg) or a vehicle is given to distinct groups of male wild-type (N = 7) and Gria1^−/− mice (N = 7) after they undergo the same procedure as in Experiment 1A. The process used in Experiment 1B is then repeated in Experiment 1C to examine the possible effects of increased proactive interference. The drug dose (30 mg/kg) and the mice are used, but a modified testing protocol is used this time, reducing the interval between trials to 20 s. Rats: Two experiments are conducted. In the first experiment, rats kept in their home cages or rats exposed to two hours of immobilization stress in plastic cones are compared for the effects of LY354740 (10 mg/kg, i.p., neutralized to a pH ~ 7.4) or vehicle (0.9% saline neutralized to pH ~ 7.4) (n = 7, cage control/vehicle; n = 7, cage control/LY354740; n = 6, stress/vehicle; n = 6, stress/Eglumegad (LY354740)). In the second experiment, rats given a 2-hour immobilization stress are compared to rats given vehicle in their home cages, or two lower doses of LY354740 (1 and 3 mg/kg, i.p.) or vehicle (n = 4 for all groups). Fifteen minutes before they are placed in plastic cones with the open end tightly closed, all animals receive an injection of either Eglumegad (LY354740) or a vehicle. Every immobilized rat is taken to a quiet room away from the animal colony, put in a plexiglass chamber with bedding on the bottom, and then put right into a plastic cone. The rats are beheaded and placed in the plastic containers; this is done two hours later. After removal, the brains are preserved at -80°C by freezing them on dry ice.

[1]. The group II metabotropic glutamate receptor agonist LY354740 and the D2 receptor antagonist haloperidol reduce locomotor hyperactivity but fail to rescue spatial working memory in GluA1 knockout mice. Eur J Neurosci. 2017 Apr;45(7):912-921.

[2]. Levels of the Rab GDP dissociation inhibitor (GDI) are altered in the prenatal restrain stress mouse model of schizophrenia and are differentially regulated by the mGlu2/3 receptor agonists, LY379268 and LY354740. Neuropharmacology. 2014 Nov:86:133-44.

[3]. Reversal of novelty-induced hyperlocomotion and hippocampal c-Fos expression in GluA1 knockout male mice by the mGluR2/3 agonist LY354740. Neuroscience. 2013 Oct 10:250:189-200.

[4]. The mGlu2/3 receptor agonist LY354740 suppresses immobilization stress-induced increase in rat prefrontal cortical BDNF mRNA expression. Neurosci Lett. 2006 May 8;398(3):328-32.

C8H11NO4

185.17724

185.07

C, 51.89; H, 5.99; N, 7.56; O, 34.56

176199-48-7

(rel)-Eglumegad; 176027-90-0; Eglumegad hydrochloride

Solid powder

C1C[C@]([C@H]2[C@@H]1[C@@H]2C(=O)O)(C(=O)O)N

VTAARTQTOOYTES-RGDLXGNYSA-N

InChI=1S/C8H11NO4/c9-8(7(12)13)2-1-3-4(5(3)8)6(10)11/h3-5H,1-2,9H2,(H,10,11)(H,12,13)/t3-,4-,5-,8-/m0/s1

(1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid

LY354740; LY-354740; LY 354740

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~33.3 mg/mL (~180 mM)
H2O: ~6.3 mg/mL (~34.2 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (13.50 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中，混合均匀。

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配方 2 中的溶解度: 2.86 mg/mL (15.44 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶 (<60°C).

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。