An Exploration into the Non-Photic Influence of Acetylcholinesterase Inhibitors on Circadian Rhythms
Date
2020-09-24
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Abstract
While light is the dominant zeitgeber (“time giver”) for the circadian system, nonphotic cues, such as exercise and arousal, also affect circadian rhythmicity. Our lab has reported that cholinergic innervation of the suprachiasmatic nucleus arising from the basal forebrain is both necessary and sufficient for phase shifting circadian rhythms in a nonphotic manner. Therefore, the present study investigated a new avenue for modulating cholinergic activity in a less invasive manner by testing whether enhancing acetylcholine neurotransmission with acetylcholinesterase (AChE) inhibitors will cause nonphotic-like phase shifts of the circadian system. Three different AChE inhibitors were explored (Donepezil, Rivastigmine, and Tacrine) at varying doses. First, Syrian hamsters were housed in constant darkness (DD), and were administered an intraperitoneal (IP) injection of one of the AChE inhibitors or vehicle control in counterbalanced order six hours before their activity onset, a phase when nonphotic treatments elicit phase advances. The second hypothesis was that nonphotic phase shifts elicited by AChE inhibitor administration requires acetylcholine activity at the SCN. Hamsters were given a microinjection of either saline or the acetylcholine antagonist Atropine to the SCN 10 minutes prior to a CT6 injection of donepezil (10mg/kg). In experiment one, Donepezil at 10mg/kg had the most robust phase advances relative to the controls. In experiment two, the results were mixed with no significant differences were found between conditions, including the baseline measurement of Donepezil/control.
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Keywords
Acetylcholine, Suprachiasmatic Nucleus, Non-photic, Circadian
Citation
Jamani, N. F. (2020). An Exploration into the Non-Photic Influence of Acetylcholinesterase Inhibitors on Circadian Rhythms (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.