scholarly journals Selective pharmacological blockade of the 5-HT7 receptor attenuates light and 8-OH-DPAT induced phase shifts of mouse circadian wheel running activity

Author(s):  
Jonathan Shelton ◽  
Sujin Yun ◽  
Susan Losee Olson ◽  
Fred Turek ◽  
Pascal Bonaventure ◽  
...  
2004 ◽  
Vol 287 (5) ◽  
pp. R1194-R1201 ◽  
Author(s):  
C. S. Colwell ◽  
S. Michel ◽  
J. Itri ◽  
W. Rodriguez ◽  
J. Tam ◽  
...  

Previous studies indicate that light information reaches the suprachiasmatic nucleus through a subpopulation of retinal ganglion cells that contain both glutamate and pituitary adenylyl cyclase-activating peptide (PACAP). Although the role of glutamate in this pathway has been well studied, the involvement of PACAP and its receptors is only beginning to be understood. To investigate the functions of PACAP in vivo, we developed a mouse model in which the gene coding for PACAP was disrupted by targeted homologous recombination. RIA was used to confirm a lack of detectable PACAP protein in these mice. PACAP-deficient mice exhibited significant impairment in the magnitude of the response to brief light exposures with both light-induced phase delays and advances of the circadian system impacted. This mutation equally impacted phase shifts induced by bright and dim light exposure. Despite these effects on phase shifting, the loss of PACAP had only limited effects on the generation of circadian oscillations, as measured by rhythms in wheel-running activity. Unlike melanopsin-deficient mice, the mice lacking PACAP exhibited no loss of function in the direct light-induced inhibition of locomotor activity, i.e., masking. Finally, the PACAP-deficient mice exhibited normal phase shifts in response to exposure to discrete dark treatments. The results reported here show that the loss of PACAP produced selective deficits in the light response of the circadian system.


1983 ◽  
Vol 244 (1) ◽  
pp. R93-R105 ◽  
Author(s):  
F. C. Davis ◽  
J. M. Darrow ◽  
M. Menaker

The circadian pacemaker that underlies the wheel-running activity of hamsters was studied in males and females. Sex differences were found in the mechanism by which the pacemaker entrains to light-dark cycles and in the timing of activity onset. When exposed to a light-dark cycle with a period of 24.75 h (with 1 h of light/cycle), males show a greater ability to maintain entrainment than do females. This difference in the upper limit of entrainment appears due to a sex difference in the magnitude of light-induced phase shifts. A small difference in free-running period may also contribute to the sex difference in entrainment. Two weeks after castration of adults, the sex difference in entrainment is not affected, indicating that the difference does not depend on circulating gonadal steroids or on estrous cyclicity of the female. However, castration of females at an early age increases their ability to entrain, whereas long-term castration of males seems to reduce entrainment ability. During entrainment to a 24-h light-dark cycle (LD 14:10), females were found to begin their daily activity before males and before castrated females. This difference is consistent with a sex difference in the magnitude of light-induced phase shifts and in entrainment of the pacemaker. However, evidence is given that the sex difference in activity onset might also be caused by a sex difference in the relationship of locomotor activity to the pacemaker in intact males and females.


2006 ◽  
Vol 291 (6) ◽  
pp. R1808-R1816 ◽  
Author(s):  
Tammy J. Jechura ◽  
Megan M. Mahoney ◽  
Cheryl D. Stimpson ◽  
Theresa M. Lee

Reentrainment following phase shifts of the light-dark (LD) cycle is accelerated in Octodon degus in the presence of olfactory social cues (i.e., odors) produced by conspecifics. However, not all odors from conspecifics were effective in facilitating reentrainment after a phase advance. In the current experiments, we examined whether nonanimal odors, odors from another species, or conspecific odors, including those manipulated by steroid hormones, can cause the same increased reentrainment of wheel-running activity as odors from an intact, adult female degu. A variety of odors, each selected to probe a particular aspect of the reentrainment acceleration phenomenon, were presented to a group of phase-shifting female degus. The shifting females (test animals) responded to odors of intact, female degu donors with decreased reentrainment time, but odors of ovariectomized (OVX), OVX with a single hormone replacement capsule (estradiol or progesterone) or phase-shifting females had no effect. Multiple males were effective odor donors, whereas a single male was ineffective in earlier studies. Rats and cloves were not effective in accelerating reentrainment. Furthermore, odors from rats delayed reentrainment. We conclude that the odors that effectively accelerate degu reentrainment after a phase advance of the LD cycle are species specific. We also report that repeated phase shifts, followed by complete recovery of phase relationships, do not alter the rate of recovery from a phase shift over time. These data suggest that in O. degus, a social species, odors may reinforce and strengthen the salience of the photic zeitgeber and/or facilitate synchronization of rhythms between animals.


1985 ◽  
Vol 248 (2) ◽  
pp. R181-R189 ◽  
Author(s):  
J. L. Blank ◽  
C. Desjardins

The reproductive responses of two species of wild rodents, house mice and deer mice, were evaluated following a 30% reduction in food intake for 5 wk. These animal models were chosen as prototypes of other rodent species because each employs unique functional adjustments when confronted with reduced resources in their natural habitats. Modest inanition failed to alter pituitary-testicular function in house mice; neither spermatogenesis nor plasma concentrations of luteinizing hormone (LH) and testosterone were modified. In sharp distinction, deer mice exposed to restricted food intake showed significant reductions in plasma LH and testosterone and an accompanying loss in spermatogenesis. Reduced food intake also caused pronounced shifts in the temporal organization and amount of wheel-running activity in both animal models, albeit in a dichotomous fashion. House mice exhibited the same amount of wheel-running activity throughout inanition, but the diel periodicity of locomotor behavior was shifted from the dark to the light period. Deer mice, in comparison, significantly curtailed wheel-running activity during the dark hours but ran in precise phase relationship with the light-dark cycle. Taken together, our results establish that the male reproductive system and its supporting neuroendocrine and behavioral correlates can be disrupted by modest levels of food restriction in certain animal models.


2009 ◽  
Vol 39 (1) ◽  
pp. 47-55 ◽  
Author(s):  
He S. Yang ◽  
Martha H. Vitaterna ◽  
Aaron D. Laposky ◽  
Kazuhiro Shimomura ◽  
Fred W. Turek

There is considerable evidence for a genetic basis underlying individual differences in spontaneous physical activity in humans and animals. Previous publications indicate that the physical activity level and pattern vary among inbred strains of mice and identified a genomic region on chromosome 13 as quantitative trait loci (QTL) for physical activity. To confirm and further characterize the role of chromosome 13 in regulating daily physical activity level and pattern, we conducted a comprehensive phenotypic study in the chromosome 13 substitution strain (CSS-13) in which the individual chromosome 13 from the A/J strain was substituted into an otherwise complete C57BL/6J (B6) genome. The B6 and A/J parental strains exhibited pronounced differences in daily physical activity, sleep-wake structure, circadian period and body weight. Here we report that a single A/J chromosome 13 in the context of a B6 genetic background conferred a profound reduction in both total cage activity and wheel-running activity under a 14:10-h light-dark cycle, as well as in constant darkness, compared with B6 controls. Additionally, CSS-13 mice differed from B6 controls in the diurnal distribution of activity and the day-to-day variability in activity onset. We further performed a linkage analysis and mapped a significant QTL on chromosome 13 regulating the daily wheel running activity level in mice. Taken together, our findings indicate a QTL on chromosome 13 with dramatic and specific effects on daily voluntary physical activity, but not on circadian period, sleep, or other aspects of activity that are different between B6 and A/J strains.


2010 ◽  
Vol 109 (3) ◽  
pp. 623-634 ◽  
Author(s):  
J. Timothy Lightfoot ◽  
Larry Leamy ◽  
Daniel Pomp ◽  
Michael J. Turner ◽  
Anthony A. Fodor ◽  
...  

Previous genetic association studies of physical activity, in both animal and human models, have been limited in number of subjects and genetically homozygous strains used as well as number of genomic markers available for analysis. Expansion of the available mouse physical activity strain screens and the recently published dense single-nucleotide polymorphism (SNP) map of the mouse genome (≈8.3 million SNPs) and associated statistical methods allowed us to construct a more generalizable map of the quantitative trait loci (QTL) associated with physical activity. Specifically, we measured wheel running activity in male and female mice (average age 9 wk) in 41 inbred strains and used activity data from 38 of these strains in a haplotype association mapping analysis to determine QTL associated with activity. As seen previously, there was a large range of activity patterns among the strains, with the highest and lowest strains differing significantly in daily distance run (27.4-fold), duration of activity (23.6-fold), and speed (2.9-fold). On a daily basis, female mice ran further (24%), longer (13%), and faster (11%). Twelve QTL were identified, with three (on Chr. 12, 18, and 19) in both male and female mice, five specific to males, and four specific to females. Eight of the 12 QTL, including the 3 general QTL found for both sexes, fell into intergenic areas. The results of this study further support the findings of a moderate to high heritability of physical activity and add general genomic areas applicable to a large number of mouse strains that can be further mined for candidate genes associated with regulation of physical activity. Additionally, results suggest that potential genetic mechanisms arising from traditional noncoding regions of the genome may be involved in regulation of physical activity.


1999 ◽  
Vol 276 (4) ◽  
pp. R1078-R1086 ◽  
Author(s):  
Gabriela Klante ◽  
Karin Secci ◽  
Mireille Masson-Pévet ◽  
Paul Pévet ◽  
Berthe Vivien-Roels ◽  
...  

We investigated the possibility that strain-dependent differences in the diurnal pattern of wheel running activity rhythms are also reflected in the melatonin profiles. The inbred rat strains ACI/Ztm, BH/Ztm, and LEW/Ztm. LEW were examined for diurnal [12:12-h light-dark (LD)] wheel running activity, urinary 6-sulphatoxymelatonin (aMT6s) excretion, melatonin concentrations of plasma and pineal glands, and melatonin receptor density in the suprachiasmatic nuclei (SCN). ACI rats displayed unimodal activity patterns with a high level of activity, whereas BH and LEW rats showed multimodal activity patterns with ultradian components and reduced activity levels. In contrast, the individual daily profiles of aMT6s excretion and mean melatonin synthesis followed a unimodal time pattern in all three strains, suggesting that different output pathways of the SCN are responsible for the temporal organization of locomotor activity and pineal melatonin synthesis. In addition, melatonin synthesis at night and SCN melatonin receptor density at day were significantly higher in BH and LEW rats than in ACI rats. These results support the hypothesis of a long-term stimulating effect of melatonin on its own receptor density in the SCN.


Sign in / Sign up

Export Citation Format

Share Document