Effects of anticholinergics and cholinergic enhancers on spatial learning and locomotion in mice

Abstract

To investigate the cholinergic system’s role In learning and memory, I. utilized the Morris water maze (MWM) task, which tests spatial ability. Subjects must locate a submerged, hidden platform using the various distal cues around the room to orient themselves in space to find the escape platform. The cholinergic system regulates spatial learning and memory necessary for tasks such as the MWM and also plays a role in locomotor activity. I performed a pilot study to demonstrate that outbred strains of mice perform the MWM task effectively. I then used an outbred strain of mice, Swiss Webster, in the MWM to test the effects of a purported cholinergic enhancer and standard anticholinergics on spatial memory and on locomotor activity. Anticholinergics hinder an animal’s ability to perform spatial learning activities by blocking muscarinic acetylcholine (ACh) receptors In the neural synapses. In Experiment One, I tested the effects of the anticholinergic. Scopolamine (Scop), thereby inhibiting effects of ACh in the neural synapses. To attempt to reverse the effects of Scop, we used Schlsandrol A (SchisA), a natural acetylcholinesterase inhibitor. The drug Is thought to Improve memory formation by inhibiting the breakdown of ACh In the synapses, which increases ACh’s effect time for synaptic transmission. I found that SchisA did not reverse memory deficits Induced by Scop, In fact, the combined drug treatment group did worse than all other groups. In addition, Scop did not have as dramatic deficits on learning as expected; therefore, in Experiment Two, I tested the effects of Scop at a higher dosage along with another anticholinergic, Atropine Sulfate (AS), in the MWM. Both anticholinergics Induced learning and memory impairments; however, they Induced opposite locomotion effects with Scop Increasing and AS decreasing locomotion. Based on these results, I do not recommend further research into the possibility of SchlsA being a treatment option for ailments involving reduced cholinergic activity, such as Alzheimer’s disease. Additionally, the higher dosage of Scop should be used in studies where a learning deficit is desired, while the dosage of AS I used should be avoided In mice due to its substantial peripheral effects

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