Effect of M1 Muscarinic Receptor Activators on Locomotion in Rats Open Access

Hu, Chun (2015)

Permanent URL: https://etd.library.emory.edu/concern/etds/41687j241?locale=en
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Abstract

The hippocampus is a brain region crucial for learning and memory and is impacted in Alzheimer's disease (AD). Drugs that target specific muscarinic acetylcholine receptors represent potential therapies for improving memory in AD. Throughout the brain, M1 is the predominant post-synaptic mAChR that mediates excitatory metabotropic effects of the neurotransmitter acetylcholine. A recent study in rats found that systemic administration of the M1-specific allosteric agonist VU0364572 enhanced spatial encoding ability as measured by spatial representations of hippocampal place cells (Lebois, 2014). However, place cell activity is known to correlate with self-motion cues such as running speeds. Thus, VU0364572 may have impacted place cells directly via activation of M1 receptors in the hippocampus (or connected regions) or indirectly by influencing locomotion. The present study reanalyzed the locomotor activity from the previous study (Lebois, 2014). We found that the M1 allosteric agonist, VU0364572, the M1 potentiator, BQCA and the FDA-approved acetylcholinesterase inhibitor, Donepezil all had no significant impact on locomotor parameters including running speeds, percent time spent stationary and thigmotaxic behavior. Our findings suggest that influence of VU0364572 on neural activity in hippocampal pyramidal neurons could not simply be accounted for by differences in locomotion.

Table of Contents

1 INTRODUCTION....................................................... 1 2 METHODS............................................................... 8 3 RESULTS................................................................ 13 4 DISCUSSION........................................................... 15 5 LIST OF FIGURES..................................................... 18

6 REFERENCES........................................................... 23

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