| Background and objective: septo-hippocampal cholinergic pathway plays a crucial role in spatial memory. Lesions and pharmachological blockades of the pathway result in the deterioration in learning and memory. Scopolamine, a non-specific muscarinic receptor antagonist, can impair the spatial memory. Studies have showed that age-related impairments and scopolamine-induced impairments may operate through similar mechanisms.Experiments have discovered that extracellular Ach releasing in septal and hippocampal regions is closely associated with cognition and behavioral state of animal.Morphine can decrease acetylcholine(Ach) turnover in parietal cortex, occipital cortex, septal region and hippocampus, etc. Morphine infusion into medial septum produces memory deficit. The effect may be due, in part, to opioid inhibition of cholinergic neurons projecting to hippocampus. Naloxone, a mu-opioid receptor antagonist, can release this inhibition and reverse morphin-induced memory damage. Brain microdialysis in vivo found that naloxone could increase Ach level in hippocampus and facilitate memory retention and recall. It is obvious that opioidergic system is also involved in the regulation of septo-hippocampal cholinergic activity.Either naloxone or galanthamine, a AchE inhibitor, can ameliorate scopolamine-induced memory deficits. Data strong support that interaction between opioid and cholinergic systems influences learning and memory function. However, the mechanism of the interaction is still unclear.The question was raised whether endogenous opioid system exerts influence on choline acetyltransferase (ChAT) activity because ChAT is the only enzyme for Ach synthesis.Scopolamine, which due to its cholinergic bloking effects, is widely accepted as providing a model of cognitive impairment seen in the elderly and has been extensively used as a tool to test the efficacy of new drugs which may have cognition enhancing potential.In present study, acute and chronic effects of scopolamine on memory were assessed using Morris water maze tasks in rats. Meanwhile, pharmaceutical effects of naloxone was compared with galanthamine on scopolamine-induced impairment of spatial memory. The assumption that naloxone can increase extracellular Ach due to enhance ChAT expression was tested. Therefore, the mechanism of interaction between opioid and cholinergic system was explored.Materials and methods: the effects of a single dose of scopolamine alone and in combination with naloxone, galanthanmine were tested in working memory version of the Morris water maze in experiment 1. All naive rats were accepted the reference memory version of navigation task: on each trial, the rat was placed into the water between quadrants, with the drop location changing for each trial but the platform location remaining constant. The rat had to swim until it found and climbed onto the escape platform. Rats were guided to the platform if they failed to locate it within 60 s. The rat was allowed to stay on the platform for 15 s. Rats were trained two sessions (three trials per session) a day for 2 days. Then the training on the working memory version of navigation was followed. A delayed-matching-to sample variant of Morris water maze was adapted. Rats were tested 2 sessions per day for 4 days, with each session consisting of two trials separated by a 10s interval, during which rats can utilize working memory to locate the platform at the second trials. On day 7, all rats were divided at random into four groups (n=14) : normal group, scopolamine group, naloxone treatment group and scopolamine treatment group. The different chemical drugs were delivered intodifferent groups (i.p.) respectively prior to the sessions(the normal group rats received the same volume saline injection). Then the escape latencies were record.Level of ChAT expression in rats hippocampal subfield CA1,CA3 and in forebrain cortex were measured quantitatively by using the immunohistochemistry method and computerized image technique. Pathomorphological change...
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