Intervention effect of naloxone on scopolamine-induced impairment of spatial working memory in rats
- VernacularTitle:纳洛酮对东莨菪碱所致大鼠空间工作记忆障碍的干预效应
- Author:
Xin DUAN
;
Guangyu MA
;
Yanmei ZHANG
- Publication Type:Journal Article
- From:
Chinese Journal of Tissue Engineering Research
2005;9(20):248-251
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: The pathway of cholinergic nerve also with rich opium receptor in the septum-hippocampus areas is an important part for spatial learning memory. There is study that naloxone, an antagonist of opium receptor, can relieve the inhibition of activity of cholinergic neuron caused by opioid peptides in the medial septum and hippocampus, promote the release of acetylcholine (Ach)into synaptic cleft, and improve the impairment of spatial memory.OBJECTIVE: To investigate the intervention effect of naloxone on impairment of spatial working memory of rats induced by scopolamine, a blocker of cholinergic muscarinic receptor.DESIGN: A randomized and controlled trial taking experimental animals as subjects.SETTING: Geriatric Department of Wuzhongpei Memorial Hospital at Shunde District of Foshan City.MATERIALS: The experiment was completed from 2003 to 2004 at the Experimental Animal Center of Medical School of Shantou University. A total of 21 SD rats of clean grade were at random divided into three groups:normal group, scopolamine group and naloxone group (scopolamine and naloxone), with 7 in each group. Build up of Morris water maze: A circular rubber pool, 2 m diameter and 55 cm height, with 30 cm depth of water at20℃-22℃, was built up. At the center of its southeast quadrant, a cylinder platform installed, which was 12 cm in diameter and 1.5 cm below the water surface, the only place for rats to escape death. The water of the pool was covered with bits of white polythene. In the house, there were light tubes, windows and tables in fixed place served as the outside cues of the pool. On the four walls of the pool, there were several randomly-hung and eye-catching markers as inside cues.METHODS: Medicines were intraperitoneally given 30 minutes before the experiment for rats in each group, scopolamine 0.4 mg/kg and naloxone 3mg/kg in two treatment groups, the equal volume saline in normal group.Then escape latencies of rats were recorded for two successive trials through a delayed-matching\task in self-made Morris water maze. After the Morris water maze examination, all rats were put to death, the tissue of left brain was selected, conventionally treated and sliced. The expression level of cholinacetyltranslase (ChAT) in areas of hippocampus and prefrontal lobe were quantitatively assayed by immunohistochemistry and the computerized image technique. At the same time, the tissue of right brain in two rats of each group was selected, the hippocampus was immediately freed, and the change of CAI region of the hippocampus observed with electron microscope.trastructure of CA1 region of hippocampus in rats.cies of two successive trials were very significantly different in normal group[(46.4±17.7)vs (13.4±8.2)s, t =7.32, P< 0.01], and significantly different in naloxone treatment group[ (27.9±14.3)vs (9.0±3.8)s, t=3.19, P< 0.05], but not pression of ChAT in pyramidal cells in CA1 and CA3 regions of hippocampus and in neurons of prefrontal cortex of three groups was not different statisticalhippocampus in all groups was normal; However, the ultrastructure of the neuron synapsis was abnormal obviously in scopolamine group: The synaptic vesicles were markedly different in size; the vesicles obviously gathered in the part of presynaptic membrane with an enhanced density, and large and sparse in the distal part. Both presynaptic and postsynaptic membranes were indistinct and fused, synaptic cleft not clear, and postsynaptic dense materials not homogeneous, indistinct and without clear borderline.CONCLUSION: Scopolamine could impair the power of spatial working memory in rats. Naloxone could promote great release of Achin neuron synaptic vesicles into synaptic clefts, and increase the density of postsynaptic dense materials, relieve the inhibition of opioid peptide to cholinergic neuron activity in the medial septum and hippocampus, and could improve space memory injury.