Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298-0709, United States.
Neurosci Lett. 2010 Apr 12;473(3):202-7. doi: 10.1016/j.neulet.2010.02.046. Epub 2010 Feb 26.
Deficits in learning and memory have been extensively observed in animal models of fetal alcohol spectrum disorders (FASD). Here we use the Morris maze to test whether vinpocetine, a phosphodiesterase type 1 inhibitor, restores learning performance in rats exposed to alcohol during the third trimester equivalent of human gestation. Long Evans rats received ethanol (5g/kg i.p.) or saline on alternate days from postnatal day (P) 4 to P10. Two weeks later (P25), the latency to find a hidden platform was evaluated (2 trials per day spaced at 40-min inter-trial intervals) during 4 consecutive days. Vinpocetine treatment started on the first day of behavioral testing: animals received vinpocetine (20mg/kg i.p.) or vehicle solution every other day until the end of behavioral procedures. Early alcohol exposure significantly affected the performance to find the hidden platform. The average latency of ethanol-exposed animals was significantly higher than that observed for the control group. Treatment of alcohol-exposed animals with vinpocetine restored their performance to control levels. Our results show that inhibition of PDE1 improves learning and memory deficits in rats early exposed to alcohol and provide evidence for the potential therapeutic use of vinpocetine in FASD.
学习和记忆缺陷在胎儿酒精谱系障碍(FASD)的动物模型中得到了广泛观察。在这里,我们使用 Morris 水迷宫来测试磷酸二酯酶 1 抑制剂长春西汀是否能恢复在人类妊娠第三个月等效期暴露于酒精的大鼠的学习表现。长爪沙鼠在出生后第 4 天到第 10 天(P)每隔一天接受乙醇(5g/kg 腹腔注射)或生理盐水。两周后(P25),评估寻找隐藏平台的潜伏期(每天进行 2 次试验,间隔 40 分钟),持续 4 天。长春西汀治疗从行为测试的第一天开始:动物每隔一天接受长春西汀(20mg/kg 腹腔注射)或载体溶液,直到行为程序结束。早期酒精暴露显著影响寻找隐藏平台的表现。乙醇暴露动物的平均潜伏期明显高于对照组。用长春西汀治疗酒精暴露的动物恢复了它们的表现,达到了对照组的水平。我们的研究结果表明,抑制 PDE1 可改善早期暴露于酒精的大鼠的学习和记忆缺陷,并为长春西汀在 FASD 中的潜在治疗用途提供了证据。