title: Histidine enhances carbamazepine action against seizures and improves spatial memory deficits induced by chronic transauricular kindling in rats.
abstract: OBJECTIVE
  To investigate whether histidine can enhance the anticonvulsant efficacy of carbamazepine (CBZ) and simultaneously improve the spatial memory impairment induced by transauricular kindled seizures in Sprague-Dawley rats.
  
  
  METHODS
  Chronic transauricular kindling was induced by repeated application of initially subconvulsive electrical stimulation through ear-clip electrodes once every 24 h until the occurrence of 3 consecutive clonic-tonic seizures. An 8-arm radial maze (4 arms baited) was used to measure spatial memory, and histamine and gamma-amino-butyric acid levels were measured by high performance liquid chromatography (HPLC).
  
  
  RESULTS
  Chronic transauricular kindling produced a significant impairment of spatial memory and a marked decrease in histamine content in the hypothalamus, the brainstem, and the hippocampus. Injection of histidine (1000 mg/kg or 1500 mg/kg, ip) significantly inhibited transauricular kindled seizures. Injection of histidine at lower doses (200 mg/kg or 500 mg/kg, ip) had no appreciable anticonvulsant effect when administered alone, whereas it significantly potentiated the protective effects of CBZ against kindled seizures. CBZ had no ameliorative effect on memory deficit, but, in contrast, histidine (200 mg/kg or 500 mg/kg, ip) alone or co-administered with CBZ significantly ameliorated the memory deficits induced by the seizures.
  
  
  CONCLUSIONS
  Chronic transauricular kindling is a very useful animal model for evaluating memory deficits associated with epilepsy, and histidine has both a potentiate effect on the anticonvulsant efficacy of CBZ and an ameliorative effect on the spatial memory deficits induced in this model. Histidine at a specific dosage range might serve as a beneficial adjuvant for the clinical treatment of epilepsy, especially when accompanied by impaired spatial memory.
authors.affiliation: Department of Pharmacology, Zhejiang University, Hangzhou 310031, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Chun-lei
authors.initials: CL
authors.lastname: Jin
authors.forename: Li-sha
authors.initials: LS
authors.lastname: Xu
authors.forename: Zheng-bin
authors.initials: ZB
authors.lastname: Zhu-Ge
authors.forename: Li-xia
authors.initials: LX
authors.lastname: Yang
authors.forename: Lu-ying
authors.initials: LY
authors.lastname: Liu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D002220:Carbamazepine / Q000494:pharmacology*; D004357:Drug Synergism; D006624:Hippocampus / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D006639:Histidine / Q000494:pharmacology*; D007031:Hypothalamus / Q000378:metabolism; D007696:Kindling, Neurologic; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; D006639:Histidine; D006632:Histamine