Ponnusamy Ravikumar, Pradhan Nithyananda
Department of Psychopharmacology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India.
Behav Pharmacol. 2006 Nov;17(7):573-80. doi: 10.1097/01.fbp.0000236268.79923.18.
Long-term use of antiepileptic drugs is common in the treatment of epilepsy. Clinical reports exist of cognitive impairment attributed to antiepileptic drugs. Hence, this study evaluates the effect of chronic administration of one antiepileptic drug, ethosuximide, on spatial and fear learning and memory in nonepileptic rats. High performance liquid chromatography with electrochemical detection was used for quantification of glutamate, glycine, taurine, gamma-aminobutyric acid, dopamine, and serotonin in the frontal cortex and hippocampus to elucidate the neurobiological basis of the effect of ethosuximide on learning and memory. We found that 21 days of ethosuximide treatment produced negative effects on fear memory (passive avoidance) at all doses (100, 200 and 250 mg/kg body weight), but had no effect on spatial learning (T-maze). Fear memory impairment was associated with decreased hippocampal dopamine levels. Ethosuximide (at all doses) had a minimal effect on the GABAergic and glutamatergic systems in all brain regions studied, with the exception of elevated levels of gamma-aminobutyric acid in the frontal cortex with the 250 mg/kg body weight dose. We have shown that long-term administration of ethosuximide adversely affects fear memory, but does not affect spatial learning and memory.
长期使用抗癫痫药物在癫痫治疗中很常见。有临床报告称抗癫痫药物会导致认知障碍。因此，本研究评估了一种抗癫痫药物乙琥胺长期给药对非癫痫大鼠空间学习和恐惧学习及记忆的影响。采用高效液相色谱-电化学检测法对额叶皮质和海马体中的谷氨酸、甘氨酸、牛磺酸、γ-氨基丁酸、多巴胺和5-羟色胺进行定量分析，以阐明乙琥胺对学习和记忆影响的神经生物学基础。我们发现，乙琥胺治疗21天对所有剂量（100、200和250毫克/千克体重）的恐惧记忆（被动回避）均产生负面影响，但对空间学习（T迷宫）没有影响。恐惧记忆受损与海马体多巴胺水平降低有关。除250毫克/千克体重剂量使额叶皮质中的γ-氨基丁酸水平升高外，乙琥胺（所有剂量）对所研究的所有脑区的γ-氨基丁酸能和谷氨酸能系统影响极小。我们已经表明，长期给予乙琥胺会对恐惧记忆产生不利影响，但不会影响空间学习和记忆。
