The Depressive Phenotype Induced in Adult Female Rats by Adolescent Exposure to THC is Associated with Cognitive Impairment and Altered Neuroplasticity in the Prefrontal Cortex
The Depressive Phenotype Induced in Adult Female Rats by Adolescent Exposure to THC is Associated with Cognitive Impairment and Altered Neuroplasticity in the Prefrontal Cortex
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DOI：
10.1007/s12640-009-9031-3
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发表时间：
2009-05-01
影响因子：
3.7
通讯作者：
Parolaro, D.
中科院分区：
文献类型：
--
作者：
Rubino, T.;Realini, N.;Parolaro, D.
我们最近证明，Delta（9）-四氢大麻酚（THC）长期给药雌性青春期大鼠诱导情绪回路的改变，最终导致成年后的抑郁样行为。由于认知功能障碍是抑郁症的主要组成部分，我们评估了这些动物成年后不同形式的记忆。青春期雌性大鼠在出生后35至45天（PND）用THC或其载体处理，并保持不受干扰直到其成年（75 PND），此时使用被动回避和径向迷宫任务评估厌恶和空间记忆。在厌恶记忆中没有发现改变，但是在径向迷宫中，THC预处理的动物表现出比载体更差的表现，表明空间工作记忆的缺陷。为了将记忆障碍与改变的神经可塑性相关联，研究了海马和前额叶皮层中标记蛋白的水平，海马和前额叶皮层是与学习和记忆最相关的区域。在THC预处理大鼠的前额叶皮层中发现突触体蛋白和PSD 95蛋白的显著减少，在海马中没有改变。最后，对前额叶皮层突触的蛋白质组学分析显示，存在活性较低的突触，其特征在于维持正常突触效率的能力降低。这张照片证明了THC诱导的抑郁表型中存在认知障碍。
We recently demonstrated that Delta(9)-tetrahydrocannabinol (THC) chronic administration in female adolescent rats induces alterations in the emotional circuit ending in depressive-like behavior in adulthood. Since cognitive dysfunction is a major component of depression, we assessed in these animals at adulthood different forms of memory. Adolescent female rats were treated with THC or its vehicle from 35 to 45 post-natal days (PND) and left undisturbed until their adulthood (75 PND) when aversive and spatial memory was assessed using the passive avoidance and radial maze tasks. No alteration was found in aversive memory, but in the radial maze THC pre-treated animals exhibited a worse performance than vehicles, suggesting a deficit in spatial working memory. To correlate memory impairment to altered neuroplasticity, level of marker proteins was investigated in the hippocampus and prefrontal cortex, the most relevant areas for learning and memory. A significant decrease in synaptophysin and PSD95 proteins was found in the prefrontal cortex of THC pre-treated rats, with no alterations in the hippocampus. Finally, proteomic analysis of the synapses in the prefrontal cortex revealed the presence of less active synapses characterized by reduced ability in maintaining normal synaptic efficiency. This picture demonstrates the presence of cognitive impairment in THC-induced depressive phenotype.