Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 9, Pages 3519-3524Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0813366106
Keywords
mouse; suprachiasmatic nucleus; psychostimulant
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Funding
- NIDA NIH HHS [F32DA024542, F32 DA024542] Funding Source: Medline
- NIDDK NIH HHS [T32 DK007646, T32DK007646] Funding Source: Medline
- NIMH NIH HHS [P50 MH074924, 1P50MH074924] Funding Source: Medline
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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.
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