Journal of Neuroscience, Vol 13, 1454-1459, Copyright © 1993 by Society for Neuroscience
Phase-shifting mechanisms in the mammalian circadian system: new light on the carbachol paradox
CS Colwell, CM Kaufman and M Menaker
Department of Biology, University of Virginia, Charlottesville 22901.
A variety of evidence now suggests that excitatory amino acid receptors
mediate the effects of light on the circadian system of mammals. However,
the ACh agonist carbachol is the only agent that has been reported to
"mimic" the phase-shifting effects of light in vivo. Because the other
published evidence for the involvement of ACh in light-mediated phase
shifts is weak, we have referred to this situation as "the carbachol
paradox." In the present study, we found that the administration of NMDA
receptor antagonists could prevent carbachol- induced phase shifts of the
circadian rhythm of wheel-running activity recorded from the hamster. In
addition, we found that carbachol-induced phase shifts, unlike those
produced by light, are not accompanied by induction of Fos-like
immunoreactivity in the suprachiasmatic nucleus (SCN). Our data are simply
explained by the assumption that the intraventricular administration of
carbachol causes phase shifts through a pathway distinct from that of
light. Alternatively, if carbachol is acting via the light input pathway,
then it must do so by a mechanism independent of Fos induction in the SCN.
In either case, elucidating the mechanisms by which carbachol acts in the
circadian system may provide novel insights into the cellular events by
which phase shifts are generated.
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