THE EFFECTS OF ANTICHOLINERGIC AGENTS AND ALPHA BUNGAROTOXIN ON CIRCADIAN REGULATION IN THE LABORATORY RAT (SUPRACHIASMATIC NUCLEUS, HYPOTHALAMUS, BIOLOGICAL RHYTHMS)
Abstract
In the laboratory rat many behavioral and physiological circadian rhythms are regulated by the suprachiasmatic nuclei (SCN) which are located in the anterior hypothalamus. A central event in the synchronization of mammalian rhythms is the communication of light/dark cycle information from the retina to the SCN. It has been hypothesized that acetylocholine (ACh) is the chemical mediator of light's entraining action on circadian pacemakers. If this were the case, then it should be possible to block the phase-shifting effects of light on rhythms by blocking cholinergic neurotransmission. I have tested this possibility and have shown that depletion of brain ACh stores by central infusion of hemicholinium does not prevent the circadian phase-shifting effects of light pulses. Animals treated with a muscarinic ACh receptor blocker (atropine) also had normal responses to light pulses. These data do not support the view that ACh is the primary mediator of photoentrainment in the rat. I have also examined hypothalamic alpha bungarotoxin (BTX) receptors and circadian regulation. Although BTX has traditionally been used as a label for putative nicotinic ACh receptors in the brain, it is now apparent that it binds to receptor sites not related to cholinergic systems. Using autoradiographic methods, I have evaluated the distribution of BTX receptors in the suprachiasmatic area. BTX binding was most intense dorsal and lateral to the SCN in a region through which SCN efferent pathways project. There was no effect of the time of day on the pattern of BTX binding. Finally, I have demonstrated that when BTX is infused into the suprachiasmatic area, it reliably induces phase and period changes in rat locomotor activity rhythms. These data represent the first report of behavioral alterations induced by exogenously administered BTX. At any given phase of injection, the direction of shifts incurred by BTX was not predictable. BTX may cause circadian perturbations by binding to the SCN efferent pathway dorsolateral and caudal to the nuclei. It is not likely that the behavioral effects of BTX reported here occur through an ACh-dependent pathway.
Recommended Citation
PAULY, JAMES RICHARD, "THE EFFECTS OF ANTICHOLINERGIC AGENTS AND ALPHA BUNGAROTOXIN ON CIRCADIAN REGULATION IN THE LABORATORY RAT (SUPRACHIASMATIC NUCLEUS, HYPOTHALAMUS, BIOLOGICAL RHYTHMS)" (1986). Dissertations (1962 - 2010) Access via Proquest Digital Dissertations. AAI8708744.
https://epublications.marquette.edu/dissertations/AAI8708744