Chronic treatment with a GPR30 antagonist impairs acquisition of a spatial learning task in young female rats.
Chronic treatment with a GPR30 antagonist impairs acquisition of a spatial learning task in young female rats.
复制标题
DOI：
10.1016/j.yhbeh.2012.07.004
复制
发表时间：
2012-09
影响因子：
3.5
通讯作者：
Gibbs, R. B.
中科院分区：
文献类型：
--
作者：
Hammond, R.;Nelson, D.;Kline, E.;Gibbs, R. B.
我们推测雌二醇对认知能力的有益作用可能是通过GPR 30介导的，GPR 30是雌激素的假定膜靶点。最近，我们发现，管理的选择性GPR 30激动剂（G-1）卵巢切除大鼠增强收购的延迟匹配位置（ESTA）T-迷宫任务和增加钾刺激的乙酰胆碱释放在海马体，类似于雌二醇（E2）。本研究测试是否与选择性GPR 30拮抗剂（G-15）治疗会损害空间学习的性腺完整的大鼠和卵巢切除（OVX）大鼠与E2治疗。正如预测的那样，G-15剂量依赖性损害性腺完整的大鼠和OVX大鼠E2治疗的前列腺获得。G-15特别降低了收购率，这种效果与增加倾向，采取一个持续的转折。相比之下，最高剂量的单独G-15对OVX对照中的细胞获得没有显著影响。的影响是任务依赖性的，类似的G-15的影响，没有观察到在性腺完整的大鼠测试的操作性歧视/反转学习任务的动机相同的食物奖励。这表明，对食物获取的影响不是由于对食物动机的影响。G-15对海马神经元获取的影响与先前发表的研究结果相似，表明海马选择性胆碱能去神经支配产生了显著的损伤。这些数据表明，GPR 30可以发挥重要的作用，在调解雌二醇对空间学习的影响，可能是通过调解雌二醇对基底前脑胆碱能功能的影响。
We hypothesize that the beneficial effects estradiol on cognitive performance may be mediated through GPR30, a putative membrane target of estrogens. Recently we showed that administration of a selective GPR30 agonist (G-1) to ovariectomized rats enhanced acquisition of a delayed matching-to-position (DMP) T-maze task and increased potassium-stimulated acetylcholine release in the hippocampus, similar to estradiol (E2). The present study tested whether treating with a selective GPR30 antagonist (G-15) would impair spatial learning in gonadally intact rats and in ovariectomized (OVX) rats treated with E2. As predicted, G-15 dose-dependently impaired DMP acquisition both in gonadally intact rats and in OVX rats treated with E2. G-15 specifically reduced the rate of acquisition, and this effect was associated with an increased predisposition to adopt a persistent turn. In contrast, G-15 alone at the highest dose had no significant effect on DMP acquisition in OVX controls. The effects were task dependent, as similar effects of G-15 were not observed in gonadally intact rats tested on an operant discrimination/reversal learning task motivated by the same food reward. This suggests that the effects on DMP acquisition were not due to effects on motivation for food. Effects of G-15 on DMP acquisition were similar to previously published work showing significant impairment produced by selective cholinergic denervation of the hippocampus. These data suggest that GPR30 can play an important role in mediating the effects of estradiol on spatial learning, possibly by mediating estradiol effects on basal forebrain cholinergic function.
登录
查看更多内容
影响因子：
3.2
作者：
Bohacek, J.;Bearl, A. M.;Daniel, J. M.
通讯作者：
Daniel, J. M.
影响因子：
3.8
作者：
Fitz, Nicholas F.;Gibbs, Robert B.;Johnson, David A.
通讯作者：
Johnson, David A.
影响因子：
--
作者：
Filardo, EJ;Quinn, JA;Bland, KI
通讯作者：
Bland, KI
影响因子：
3.5
作者：
Daniel, JM;Fader, AJ;Dohanich, GP
通讯作者：
Dohanich, GP
影响因子：
3.5
作者：
Frick KM
通讯作者：
Frick KM