The methamphetamine-sensitive circadian oscillator does not employ canonical clock genes.
The "master clock" in the suprachiasmatic nucleus (SCN) of the hypothalamus controls most behavioral, physiological, and molecular circadian rhythms in mammals. However, there are other, still unidentified, circadian oscillators that are able to carry out some SCN functions. Here we show that one of these, the methamphetamine-sensitive circadian oscillator (MASCO), which generates behavioral rhythms in the absence of the SCN, is based on an entirely different molecular mechanism. We tested mice lacking, or with mutations of, genes that form the canonical circadian machinery. In all cases, animals that were arrhythmic as a consequence of genetic defect expressed circadian locomotor rhythms when treated with methamphetamine. These results strongly support the hypothesis that the mechanism generating MASCO does not involve the molecular feedback loops that underlie canonical circadian rhythmicity. The properties of MASCO may provide insight into the evolution of circadian mechanisms. Importantly, MASCO may play a role in addiction to psychostimulants.
Mohawk
Jennifer A
JA
Department of Biology, University of Virginia, Charlottesville VA 22904, USA.
Baer
Matthew L
ML
Menaker
Michael
M
D000818:Animals; D056926:CLOCK Proteins; D002940:Circadian Rhythm / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D013379:Substrate Specificity; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
D015534:Trans-Activators; D008694:Methamphetamine; D056926:CLOCK Proteins; C538944:Clock protein, mouse