IFEC, Conicet, Departamento de Farmacologia, Facultad de Ciencias Quimicas, Unc, Haya de la Torre Y Medina Allende, 5000, Cordoba, Argentina.
Synapse. 2010 Oct;64(10):742-53. doi: 10.1002/syn.20788.
Hippocampus is a limbic structure that participates in learning and memory formation. Specifically the dentate gyrus has been described as a hippocampal subregion with high rates of plasticity and it is targeted by different psychoactive drugs modulating synaptic plasticity. Repeated cocaine administration induces sensitization to the locomotor effects and it is believed that sensitization involves the same mechanisms of drug seeking and relapse. Although, the mechanisms underlying sensitization is not fully understood. In this work we investigated the impact of repeated intraperitoneal administration of cocaine (15 or 20 mg/kg/day along 5 or 15 days respectively; and 15 mg/kg/day along 5 day followed by a challenge dose after three days of withdrawal) on the dentate gyrus synaptic plasticity, differentiating between sensitized and nonsensitized rats. Furthermore, we correlated changes on the hippocampal synaptic plasticity to memory retention. Our results revealed that the prevalence of cocaine sensitization (around 50%) was identical in all protocols used. The results found in the threshold to generate LTP were similar for all protocols used, being the threshold values cocaine-treated groups (sensitized and nonsensitized) significantly reduced compared to controls, observing the highest reduction in the sensitized group. Moreover, we observed a facilitated retention of recent memory formation only in sensitized animals the nonsensitized subjects remained at the control levels. In conclusion, sensitization to cocaine generates a high efficiency of hippocampal synaptic plasticity that may underlie the aberrant engagement of learning processes occurred during drug addiction.
海马体是参与学习和记忆形成的边缘结构。具体来说，齿状回已被描述为具有高可塑性的海马亚区，它是不同的精神活性药物调节突触可塑性的靶点。重复给予可卡因会引起运动效应的敏化，并且据信敏化涉及到寻求药物和复发的相同机制。尽管如此，敏化的机制尚未完全理解。在这项工作中，我们研究了重复腹膜内给予可卡因（15 或 20mg/kg/天，分别持续 5 或 15 天；15mg/kg/天，持续 5 天，然后在戒断 3 天后给予挑战剂量）对齿状回突触可塑性的影响，区分敏化和非敏化大鼠。此外，我们将海马突触可塑性的变化与记忆保留相关联。我们的结果表明，所有使用的方案中可卡因敏化的发生率（约 50%）相同。用于产生 LTP 的阈值的结果对于所有使用的方案都是相似的，与对照组相比，可卡因处理组（敏化和非敏化）的阈值显着降低，在敏化组中观察到最大降低。此外，我们仅在敏化动物中观察到近期记忆形成的保留得到促进，而非敏化受试者仍保持在对照水平。总之，可卡因敏化会产生高效的海马突触可塑性，这可能是成瘾期间学习过程异常参与的基础。
