Prickaerts J, Blokland A, Bothmer J, Honig W, Markerink-Van Ittersum M, Jolles J
Department of Psychiatry and Neuropsychology, European Graduate School of Neuroscience EURON, Maastricht University, The Netherlands.
Neurochem Int. 1998 Nov;33(5):435-43. doi: 10.1016/s0197-0186(98)00047-3.
In the present study we investigated the effects of acute treatment with acetyl-L-carnitine (50 mg/kg, i.v. 90 min before the sodium cyanide injection) on a sodium cyanide-induced behavioral deficit in the Morris water escape task. In a first experiment the spatial discrimination performance of the rats was found to be dose-dependently impaired after an i.c.v. injection of sodium cyanide (2.5 and 5.0 microg). Acute treatment with acetyl-L-carnitine was found to increase the behavioral deficit after sodium cyanide. These findings were replicated in a second experiment. Based on these results it can be argued that an acute administration of acetyl-L-carnitine appears to potentiate a sodium cyanide-induced behavioral deficit. An additional in vitro experiment with rat brain synaptosomes showed clear effects of administered sodium cyanide on the energy-dependent incorporation of inositol into phosphoinositides and on the ATP concentration. In vitro acetyl-L-carnitine administration had no effect on the sodium cyanide-induced energy depletion. The negative behavioral findings are in contrast with our previously found protective effect of chronic treatment with acetyl-L-carnitine (via drinking water) on the sodium cyanide-induced behavioral deficit. Since chronic acetyl-L-carnitine treatment has no effect on the phosphoinositide metabolism it was suggested that acetyl-L-carnitine may act via the formation of an ATP-independent reservoir of activated acyl groups. Thus, fatty acids as acylated derivatives can be used for reacylation processes during an acute period of energy depletion. However, we have no clear explanation for the discrepancy in behavioral results between the chronic vs acute treatment of acetyl-L-carnitine at present. Further research is needed to characterize the mechanism of action of acetyl-L-carnitine in relation to sodium cyanide.
在本研究中，我们调查了乙酰-L-肉碱急性处理（50毫克/千克，在注射氰化钠前90分钟静脉注射）对氰化钠诱导的Morris水迷宫逃避任务行为缺陷的影响。在第一个实验中，发现大鼠经脑室内注射氰化钠（2.5和5.0微克）后，其空间辨别能力呈剂量依赖性受损。乙酰-L-肉碱急性处理后，发现氰化钠诱导的行为缺陷有所增加。这些发现在第二个实验中得到了重复。基于这些结果，可以认为急性给予乙酰-L-肉碱似乎会增强氰化钠诱导的行为缺陷。另外一项用大鼠脑突触体进行的体外实验表明，给予的氰化钠对肌醇向磷酸肌醇的能量依赖性掺入以及ATP浓度有明显影响。体外给予乙酰-L-肉碱对氰化钠诱导的能量耗竭没有影响。负面的行为学结果与我们之前发现的乙酰-L-肉碱慢性处理（通过饮水）对氰化钠诱导的行为缺陷的保护作用形成对比。由于慢性乙酰-L-肉碱处理对磷酸肌醇代谢没有影响，因此有人提出乙酰-L-肉碱可能通过形成不依赖ATP的活化酰基库发挥作用。因此，脂肪酸作为酰化衍生物可在能量耗竭急性期用于再酰化过程。然而，目前我们对乙酰-L-肉碱慢性处理与急性处理行为结果差异尚无明确解释。需要进一步研究来阐明乙酰-L-肉碱与氰化钠相关的作用机制。
