Abstract
Objectives:The study was planned to determine cholinergic influence on different stages of memory - acquisition, consolidation and recall in scopolamine-induced amnesia (memory impairment) in mice.Materials and Methods:To study acquision, consolidation and recall stages of memory, we administered scopolamine (0.75, 1.5 and 3 mg/kg ip) 30 minutes and five minutes prior to first trial acquisition and consolidation and 30 minutes prior to second trial recall of passive avoidance (PA) test, respectively, in separate groups. Tacrine (5 mg/kg po) and rivastigmine (5 mg/kg po) were administered one hour prior to first trial in separate groups which received scopolamine (3 mg/kg ip) 30 minutes and five minutes prior to first trial where as the control group received vehicle only.Results:In the control group, there was a significant (P < 0.01) increase in transfer latency time (TLT) in the second trial compared to first indicating successful learning. In scopolamine treated groups, administering scopolamine 30 minutes or five minutes prior to first trial did not show any significant (P > 0.05) change in TLT whereas mice treated with scopolamine 30 minutes prior to second trial showed significant (P < 0.01) increase in TLT in second trial as compared to the first. Both tacrine and rivastigmine administration in scopolamine treated mice showed significant (P < 0.05-0.01) increase in TLT in second trial as compared to first trial while the rivastigmine treated group showed greater percentage retention compared to tacrine treated group.Conclusion:Results show that acquisition and consolidation are more susceptible to the scopolamine effects than recall. Thus, it may be concluded that cholinergic influence is more on acquisition and consolidation as compared to recall.
Highlights
Based on experimental and clinical evidences, acetylcholine (ACh) is considered the most important neurotransmitter involved in regulation of cognitive functions.[1,2] Alzheimer’s disease (AD) is the most common age related neurodegenerative disorder characterized by cognitive dysfunction with memory impairment and behavioral disturbances.[3,4] Besides the neuropathological hallmarks of the disease, neurofibrillary tangles and neuritic plaques, AD is characterized by a consistent deficit in cholinergic neurotransmission in basal forebrain
Mice treated with scopolamine at the doses of 0.75, 1.5 and 3 mg/ kg ip 30 minutes prior to first trial for acquisition did not show any significant change [P > 0.05, df = four] in transfer latency time on second trial as compared to first trial
Mice treated with scopolamine at the doses of 0.75, 1.5 and 3 mg/kg ip 30 minutes prior to second trial for recalling process showed significant increase [P < 0.01, df = four] in transfer latency time (TLT) on second trial as compared to first trial
Summary
Based on experimental and clinical evidences, acetylcholine (ACh) is considered the most important neurotransmitter involved in regulation of cognitive functions.[1,2] Alzheimer’s disease (AD) is the most common age related neurodegenerative disorder characterized by cognitive dysfunction with memory impairment and behavioral disturbances.[3,4] Besides the neuropathological hallmarks of the disease, neurofibrillary tangles and neuritic plaques, AD is characterized by a consistent deficit in cholinergic neurotransmission in basal forebrain. The cholinergic receptor agonists (muscarinic and nicotinic) and enhancers of endogenous level of ACh (synthesis promoters and inhibitors of its metabolizing enzyme) have been tried to treat senile dementia of Alzheimer type. Among the various approaches attempted to increase cholinergic activity, the inhibition of acetylcholiesterase (AChE) is the most successful one.[5] Cholinesterase inhibitors are the only class of compounds consistently proven to be efficacious in treating the cognitive and functional symptoms of AD.[6]
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