| Summary: | 博士 === 中國醫藥學院 === 中國藥學研究所 === 91 === ABSTRACT
Cognition-enhancing drugs could facilitate the performance in some kinds of animal learning and memory deficit models, including water maze, pass and active avoidance learning performances. We evaluated the cognition-enhancing effect of Rehmanniae Radix and catapol, an active constituent of Rehmanniae Radix, by using these animal models. Furthermore, we measured monoamine levels in the cortex and hippocampus of the cerebral ischemic rats and Aβ4- treated rats to demonstrate the attenuating mechanisms of Rehmanniae Radix and its constituent catalpol on the cerebral ischemia and Aβ4- induced learning and memory deficits.
The results showed that the methanolic extract of Rehmanniae Radix (RM) at the dose of 30-300 mg/kg facilitated the inhibitory avoidance response with a low stimulus in rats. Moreover, 300 mg/kg RM reversed the step-through latency (STL) shortened by scopolamine or cerebral ischemic rats. It also shortened the swimming time reaching to the hidden platform on Morris water maze spatial performance and working memory, and enhanced the swimming time spent in the target ring on reference memory in cerebral ischemic rats. The butanolic (10-30mg/kg) but not water layer of methanolic extract of Rehmanniae Radix facilitated the inhibitory avoidance response with a low stimulus. In addition, it reversed the STL shortened by scopolamine and cerebral ischemic rats, shortened the swimming time reaching to the hidden platform on Morris water maze spatial performance and working memory, and enhanced the swimming time spent in the target ring on reference memory in scopolamine-treated rats and cerebral ischemic rats.
Catalpol (10 µg/kg), the major constituent of Rehmanniae Radix reversed the STL shortened by scopolamine, cerebral ischemic rats and Aβ4- infused rats and shortened the swimming time reaching to the hidden platform on Morris water maze spatial performance and working memory. It also enhanced the swimming time spent in the target ring on reference memory in scopolamine-treated rats and cerebral ischemic rats. Catalpol (10 mg/kg s.c.) also facilitated the spatial performance of Morris water maze but not working memory in Aβ4- infused rats and improved active avoidance learning performance deficit of cerebral ischemic rats and Aβ4- infused rats .
Furthermore, we investigated the relationship between the ameliorating effect of catapol on the learning and memory and central neuronal systems. The results showed that catalpol at 10 g/brain (i.c.v.) did not ameliorate the performance impairment induced by 5, 7-DHT (25 µg/brain, intra-raphe), PROP (80 ng/brain, intrahippocampus), and YOH (80 ng/brain, intrahippocampus) on Morris water maze. However, catalpol at 10 g/brain (i.c.v) significantly improved the deficit of spatial performance induced by AF64A (3 g/brain, intrahippocampus), 6-OHDA (25 g/brain, intra-LC), SCOP (3.2 ng/brain, intrahippocampus) and PHEN (80 ng/brain, intrahippocampus).
Finally, we measured the concentration of monoamines and their metabolites in the cerebral cortex and hippocampus of cerebral ischemia rats and Aβ-(1-40)-infused rats. The results showed that cerebral ischemic rats and Aβ-(1-40)-infused rats had higher levels of DA, DOPAC in hippocampus and cortex. Catalpol reversed the deterioration of the activities of NE levels in cortex and hippocampus, it also reduced the levels of DA in the cerebral ischemic rats and Aβ-(1-40)-infused rats.
We suggested that catalpol decreased the levels of DA and increase the levels of NE in cortex and hippocampus. The ameliorating effects of catalpol on learning and memory were associated with the central catecholaminergic neuronal and central cholinergic neuronal systems and adrenergic α1 receptors but not associated with the serotonergic neuronal system.
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