Donepezil treatment restores the ability of estradiol to enhance cognitive performance in aged rats: evidence for the cholinergic basis of the critical period hypothesis.
Donepezil treatment restores the ability of estradiol to enhance cognitive performance in aged rats: evidence for the cholinergic basis of the critical period hypothesis.
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DOI：
10.1016/j.yhbeh.2009.03.003
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发表时间：
2009-06
影响因子：
3.5
通讯作者：
Johnson DA
中科院分区：
文献类型：
--
作者：
Gibbs RB;Mauk R;Nelson D;Johnson DA
最近的研究表明，在卵巢功能丧失后，雌激素提高认知能力的能力随着年龄和/或时间的推移而减弱。我们假设这在一定程度上是由于基底前脑胆碱能功能的下降。这项研究测试了胆碱酯酶抑制剂多奈哌齐是否能恢复雌二醇对年轻时切除卵巢的老年大鼠认知能力的影响。3个月龄大鼠摘除卵巢，然后进行延迟匹配T迷宫任务，然后从12-17或22-27个月龄开始进行结构联想(CA)操作条件任务。在测试前三周，大鼠开始接受多奈哌齐或赋形剂治疗。一周后，每组中的一半人也开始接受雌二醇治疗。驯化和测试在七天后开始，治疗在整个测试过程中继续进行。雌二醇单用可显著增加中年大鼠DMP的获得量，但对老年大鼠无明显影响。在两个年龄组中单独使用多奈哌齐对DMP的获取都没有影响；然而，多奈哌齐治疗恢复了雌二醇促进老年大鼠DMP获取的能力。这在很大程度上是由于在收购过程中采取持续转向策略的倾向降低了。这些相同的处理不影响中年大鼠的CA任务的获得，但对老年大鼠的反应时间有很小但显著的影响。这些数据与雌激素对认知表现的影响是任务特异性的这一观点是一致的，而且基底前脑胆碱能功能的缺陷是老年去卵巢大鼠失去雌激素对DMP获得的影响的原因。此外，数据表明，在长期激素剥夺后，从药理上增强胆碱能功能可以恢复雌二醇增强DMP任务获得的能力。多奈哌齐对其他雌激素敏感的任务是否有类似的恢复作用还有待研究。
Recent studies suggest that the ability of estradiol to enhance cognitive performance diminishes with age and/or time following loss of ovarian function. We hypothesize that this is due, in part, to a decrease in basal forebrain cholinergic function. This study tested whether donepezil, a cholinesterase inhibitor, could restore estradiol effects on cognitive performance in aged rats that had been ovariectomized as young adults. Rats were ovariectomized at 3 months of age, and then trained on a delayed matching to position (DMP) T-maze task, followed by a configural association (CA) operant condition task, beginning at 12–17 or 22–27 months of age. Three weeks prior to testing, rats started to receive either donepezil or vehicle. After one week, half of each group also began receiving estradiol. Acclimation and testing began seven days later and treatment continued throughout testing. Estradiol alone significantly enhanced DMP acquisition in middle-aged rats, but not in aged rats. Donepezil alone had no effect on DMP acquisition in either age group; however, donepezil treatment restored the ability of estradiol to enhance DMP acquisition in aged rats. This effect was due largely to a reduction in the predisposition to adopt a persistent turn strategy during acquisition. These same treatments did not affect acquisition of the CA task in middle-aged rats, but did have small but significant effects on response time in aged rats. The data are consistent with the idea that estrogen effects on cognitive performance are task specific, and that deficits in basal forebrain cholinergic function are responsible for the loss of estradiol effect on DMP acquisition in aged ovariectomized rats. In addition, the data suggest that enhancing cholinergic function pharmacologically can restore the ability of estradiol to enhance acquisition of the DMP task in very old rats following long periods of hormone deprivation. Whether donepezil has similar restorative effects on other estrogen-sensitive tasks needs to be explored.
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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：
1.9
作者：
BAXTER, MG;BUCCI, DJ;GALLAGHER, M
通讯作者：
GALLAGHER, M
影响因子：
4.7
作者：
Chappell, J;McMahan, R;Gallagher, M
通讯作者：
Gallagher, M
影响因子：
3.3
作者：
Daniel, JM;Hulst, JL;Lee, CD
通讯作者：
Lee, CD
影响因子：
5.3
作者：
Adams, MM;Morrison, JH;Gore, AC
通讯作者：
Gore, AC