Pereira de Vasconcelos A, Klur S, Muller C, Cosquer B, Lopez J, Certa U, Cassel J C
LN2C FRE 2855, Université Louis Pasteur, ULP/CNRS, Institut Fédératif de Recherche IFR 37, GDR CNRS 2905, 12 rue Goethe, F 67000 Strasbourg, France.
Neuroscience. 2006 Sep 15;141(4):1649-63. doi: 10.1016/j.neuroscience.2006.05.023. Epub 2006 Jun 22.
Reversible inactivation of the hippocampus by lidocaine or tetrodotoxin is used to investigate implications of this structure in memory processes. Crucial points related to such inactivation are the temporal and spatial extents of the blockade. We compared effects of intrahippocampal infusions of commonly-used doses of lidocaine (5 or 10 mug) or tetrodotoxin (5 or 10 ng) in rats at two post-infusion delays (5 or 30 min), using 2-deoxyglucose autoradiography to visualize local cerebral glucose metabolism, and beam-walking performance to assess motor coordination. In addition, memory retrieval was evaluated in a water maze after bilateral infusions of 10 mug lidocaine. A unilateral tetrodotoxin infusion induced dose- and time-dependent reductions of 2-deoxyglucose uptake in the vicinity of the infusion site (dorsal hippocampus: -29% to -67%) and in other ipsi- and contralateral brain regions (ventral hippocampus, lateral thalamus, cortical regions). The maximal effect was at 10 ng, at the delay of 30 min between the tetrodotoxin infusion and the 2-deoxyglucose injection. Uni- and bilateral infusions of tetrodotoxin induced dramatic motor coordination deficits. Conversely, lidocaine reduced 2-deoxyglucose uptake (-19%) in the dorsal hippocampus only at 10 mug, with weak extrahippocampal effects. Whether infused uni- or bilaterally and regardless of the dose, lidocaine did not alter motor coordination. When infused bilaterally, however, 10 microg of lidocaine impaired short-term retrieval of spatial information in a water maze. Because lidocaine i) induced a weak though significant functional blockade mainly restricted to the infusion site, ii) had no consequences on motor coordination and, nevertheless iii) altered short-term spatial memory retrieval, we conclude that acute intrahippocampal infusions of lidocaine may offer some advantages over tetrodotoxin at the doses used herein.
利多卡因或河豚毒素对海马体的可逆性失活被用于研究该结构在记忆过程中的作用。与这种失活相关的关键点是阻断的时间和空间范围。我们比较了在大鼠海马体内注射常用剂量的利多卡因（5或10微克）或河豚毒素（5或10纳克）后，在两个注射后延迟时间（5或30分钟）的效果，使用2-脱氧葡萄糖放射自显影来观察局部脑葡萄糖代谢，并通过走梁实验来评估运动协调性。此外，在双侧注射10微克利多卡因后，在水迷宫中评估记忆提取情况。单侧注射河豚毒素会导致注射部位附近（背侧海马体：-29%至-67%）以及同侧和对侧其他脑区（腹侧海马体、外侧丘脑、皮质区域）的2-脱氧葡萄糖摄取呈剂量和时间依赖性降低。最大效应出现在10纳克，在河豚毒素注射和2-脱氧葡萄糖注射之间延迟30分钟时。单侧和双侧注射河豚毒素均会导致明显的运动协调缺陷。相反，利多卡因仅在10微克时会使背侧海马体的2-脱氧葡萄糖摄取减少（-19%），对海马体外的影响较弱。无论单侧还是双侧注射，且无论剂量如何，利多卡因均不会改变运动协调性。然而当双侧注射10微克利多卡因时，会损害水迷宫中空间信息的短期提取。因为利多卡因i）诱导了一种主要局限于注射部位的微弱但显著的功能阻断，ii）对运动协调性没有影响，并且iii）改变了短期空间记忆提取，我们得出结论，在本文使用的剂量下，海马体内急性注射利多卡因可能比河豚毒素具有一些优势。
