Circadian Behavioral Rhythms in <i>Cry1/Cry2</i> Double-Deficient Mice Induced by Methamphetamine

Honma, Sato; Yasuda, Toshitaka; Yasui, Akira; Horst, Gijsbertus T. J. van der; Honma, K.

doi:10.1177/0748730407311124

Cited by 45 publications

(45 citation statements)

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“…A significant peak is observed at 29.17 h. rhythmicity. A similar finding has been reported previously by Honma et al (5). However, these investigators found that some Cry1 Ϫ/Ϫ /Cry2 Ϫ/Ϫ mice did not become rhythmic in the presence of methamphetamine, whereas all the mice we tested exhibited at least transient periods of rhythmicity.…”

Section: Discussionsupporting

confidence: 66%

“…However there is reason to believe that this may not be the case. Mice carrying the Clock⌬19 gene mutation and others in which the 2 cryptochromes have been knocked out have arrhythmic phenotypes in constant conditions but become rhythmic when given methamphetamine (5,6). These data suggest that the molecular events that underlie MASCO may differ substantially from those that generate canonical circadian oscillations.…”

mentioning

confidence: 63%

“…However, these investigators found that some Cry1 Ϫ/Ϫ /Cry2 Ϫ/Ϫ mice did not become rhythmic in the presence of methamphetamine, whereas all the mice we tested exhibited at least transient periods of rhythmicity. The concentration of methamphetamine we used was twice that used by Honma et al (5), and the difference in dose probably explains the different result. The observed free-running rhythms in Cry1 Ϫ/Ϫ /Cry2 Ϫ/Ϫ mice make it clear that cryptochromes are not necessary for the expression of MASCO, although rhythmicity is less consistent in Cry1 Ϫ/Ϫ /Cry2 Ϫ/Ϫ animals than in wild-type mice on methamphetamine.…”

Section: Discussionmentioning

confidence: 94%

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The methamphetamine-sensitive circadian oscillator does not employ canonical clock genes

Mohawk

Baer

Menaker

2009

Proc. Natl. Acad. Sci. U.S.A.

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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 methamphetaminesensitive 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.mouse ͉ suprachiasmatic nucleus ͉ psychostimulant T he dominant circadian pacemaker in the mammalian brain is contained within the suprachiasmatic nucleus (SCN) of the hypothalamus (1, 2). However, if the SCN is ablated by lesion or suppressed by constant bright light, resulting in arrhythmic locomotor behavior, circadian rhythmicity can be reconstituted with methamphetamine (3, 4). Arrhythmic, SCN-lesioned rats (SCNX) (3) and mice (4) given ad libitum access to drinking water containing a low dose of methamphetamine produce clear, robust locomotor rhythms with circadian periods that are considerably longer than those of intact animals drinking pure water. Such methamphetamine-induced rhythms continue under constant conditions as long as the drug is present in the drinking water and often for several cycles after its removal (4). These experiments, together with the appropriate controls (3, 4), demonstrate that these rhythms are not the result of a non-oscillating ''hourglass'' but rather constitute clear evidence of the existence of an effective circadian pacemaker outside the SCN. We have called this pacemaker the methamphetamine-sensitive circadian oscillator (MASCO) and are studying its properties.As yet very little is known about MASCO despite overwhelming evidence of its existence. Its location is unknown, although it would be surprising if it were not somewhere in the brain, perhaps associated with dopaminergic and/or serotonergic pathways. Parsimony would suggest that it might be generated by the same molecular feedback loops that produce circadian rhythmicity in the SCN itself and in many peripheral cells, tissues, and organs. However there is reason to believe that this may not be the case. Mice carrying the Clock⌬19 gene mutation and others in which the 2 cryptochromes have been knocked out have arrhythmic phenotypes in constant conditions but become rhythmic when given methamphetamine (5, 6). These data suggest that the molecular events that underlie MASCO...

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Section: Discussionsupporting

confidence: 66%

mentioning

confidence: 63%

Section: Discussionmentioning

confidence: 94%

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The methamphetamine-sensitive circadian oscillator does not employ canonical clock genes

Mohawk

Baer

Menaker

2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Under a LD cycle, Cry1 ) ⁄ ) ⁄ Cry2 ) ⁄ ) mice show robust nocturnal behavioral rhythms, which have been regarded as the masking of lightness and darkness . Recent studies of behavioral rhythms in Cry1 ) ⁄ ) ⁄ -Cry2 ) ⁄ ) mice showed advancement of the activity onset phase when compared to the dark onset in a 12:12 h LD cycle (Honma et al 2008) and in long photoperiods (Mrosovsky 2001). These studies (Mrosovsky 2001;Honma et al 2008) challenged the previous notion that the behavioral rhythm in Cry1 ) ⁄ ) ⁄ Cry2 ) ⁄ ) mice under the LD cycle represents a direct masking by light.…”

Section: Introductioncontrasting

confidence: 47%

“…This notion is supported by the fact obtained by the present and previous studies that wheel-running activity in Cry1 ) ⁄ ) ⁄ Cry2 ) ⁄ ) mice under the LD cycle started prior to dark onset. Such 'predark activity' has been reported in both a 12:12 h LD cycle (Honma et al 2008) and long photoperiods (Mrosovsky 2001) and systematically changes dependent on the length of photoperiod. The predark activity could not be explained by light masking, but rather suggests an oscillatory mechanism for predark onset of behavioral rhythm.…”

Section: Discussionmentioning

confidence: 99%

Loss of circadian rhythm and light‐induced suppression of pineal melatonin levels in Cry1 and Cry2 double‐deficient mice

Yamanaka¹,

Suzuki²,

Todo³

et al. 2010

Genes to Cells

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Cryptochrome 1 and 2 (Cry1 and Cry2) are considered essential for generating circadian rhythms in mammals. The role of Cry1 and Cry2 in circadian rhythm expression and acute lightinduced suppression of pineal melatonin was assessed using Cry1 and Cry2 double-deficient mice (Cry1 ) ⁄ ) /Cry2 ) ⁄ ) ) developed from the C3H strain that synthesizes melatonin. We examined the circadian variation of pineal melatonin under a 12:12-h light-dark (LD) cycle and constant darkness (DD). Light suppression of pineal melatonin concentration was analyzed by subjecting a 30-min light pulse at the peak phase of melatonin concentration. Wild-type mice showed significant rhythmicity in pineal melatonin concentration with the highest level at Zeitgeber time 22 (ZT22, where time of light on was defined as ZT0) under LD or ZT18 on the first day of DD. In contrast, Cry1 ) ⁄ ) /Cry2 ) ⁄ ) mice did not show significant circadian rhythmicity, with only a small peak observed at ZT22 in LD. Nevertheless, a significant daily variation could be observed under DD, with a small increase at ZT6 and ZT18 h. Melatonin concentration was significantly suppressed by acute light pulse at ZT22 in wild-type mice but not in Cry1 ) ⁄ ) /Cry2 ) ⁄ ) mice. The present results suggest that Cry genes are required for regulating pineal melatonin synthesis via circadian and photic signals from the suprachiasmatic nucleus of the hypothalamus (SCN).

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Circadian Clock, Reward and Addictive Behavior

Albrecht

2015

Circadian Medicine

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Circadian Behavioral Rhythms in Cry1/Cry2 Double-Deficient Mice Induced by Methamphetamine

Cited by 45 publications

References 13 publications

The methamphetamine-sensitive circadian oscillator does not employ canonical clock genes

The methamphetamine-sensitive circadian oscillator does not employ canonical clock genes

Loss of circadian rhythm and light‐induced suppression of pineal melatonin levels in Cry1 and Cry2 double‐deficient mice

Circadian Clock, Reward and Addictive Behavior

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