Tetramethylpyrazine Improves Spatial Cognitive Impairment Induced by Permanent Occlusion of Bilateral Common Carotid Arteries or Scopolamine in Rats

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Abstract
Effects of tetramethylpyrazine (TMP), a major constituent of Ligusticum chuanxiong, on spatial cognitive impairment induced by permanent occlusion of bilateral common carotid arteries (2VO) and scopolamine were investigated using 8-arm radial maze performance in rats. Permanent 2VO produced a severe learning deficit in non-pretrained rats. Daily administration of TMP (3-10 mg/kg, i.p.) from the 3rd day after permanent 2VO significantly improved the learning deficit. TMP did not influence the impairment of the retention task in the pretrained permanent 2VO rats, but it tended to reduce the number of errors elevated by 3-min delay interposition in these rats. In the scopolamine model, scopolamine (0.3 mg/kg, i.p.) significantly decreased the initial correct response and increased the number of errors. Single administration of TMP (1-3 mg/kg, i.p.) dose-dependently reversed the scopolamine-induced impairment of the maze performance. These results suggest that TMP has therapeutic potential for the treatment of dementia caused by cholinergic dysfunction and/or decrease of cerebral blood flow.