Date Thesis Awarded
Honors Thesis -- Open Access
Bachelors of Science (BS)
The cholinergic system plays a large role in regulating attentional processing. Diseases such as Alzheimer’s Disease are known to degrade cholinergic neurons and deactivate cholinergic M1 receptors. Dysfunction in the cholinergic system results in a wide range of cognitive deficits, including a decrease in attention. The cholinergic system has been a focus of drug research to help modulate acetylcholine levels in order to relieve AD symptoms. Xanomeline is a drug previously used in this endeavor that works via agonism of acetylcholine M1 and M4 receptors. Cognitive improvements of Xanomeline administration in AD are thought to be due to agonism of M1, a receptor that is widely expressed in the cortex. The present study investigated the effects of Xanomeline administration on attention to determine if M1/M4 agonism could improve sustained attention. Results of this experiment revealed that M1/M4 agonism by Xanomeline did not improve attention as predicted, in fact some measures of sustained attention reflected poorer performance. The measures that were affected suggest that agonism of M4 may have a significant impact on motivation and movement during attentional testing, and M4 agonism may have obscured any improvements on attention by agonism of M1. This study may support recent evidence that Xanomeline administration in vivo produces greater activation of M4 than M1. Future studies investigating the role of M1 in attention should focus on drugs that are more selective for the M1 receptor.
Smith, Grace, "Effects of Xanomeline on Attention in Rats" (2021). Undergraduate Honors Theses. William & Mary. Paper 1670.
Available for download on Sunday, May 14, 2023