Aging alters the phase-resetting properties of a serotonin agonist on hamster circadian rhythmicity

1995 ◽  
Vol 268 (1) ◽  
pp. R293-R298 ◽  
Author(s):  
P. D. Penev ◽  
P. C. Zee ◽  
E. P. Wallen ◽  
F. W. Turek

Serotonergic mechanisms are believed to play a considerable role in mediating the effects of photic and nonphotic stimuli on circadian rhythmicity. Because aging is associated with significant changes in the responsiveness of the rodent circadian system to major synchronizing agents in the environment, this study examined the phase-shifting effects of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin [8-OH-DPAT; 2.0, 5.0, and 8.0 mg/kg ip at circadian time 8 (CT 8)], on the 24-h activity rhythm of young (3-4 mo old) and old (18-19 mo old) golden hamsters. Aging was associated with a dramatic attenuation of the phase-shifting effects of 8-OH-DPAT in this species. The results suggest the existence of age-related deficits in the serotonergic control of mammalian circadian rhythmicity, which could interfere with the temporal adaptation of the senescent organism to its environment.

1997 ◽  
Vol 272 (2) ◽  
pp. R509-R513 ◽  
Author(s):  
P. D. Penev ◽  
F. W. Turek ◽  
E. P. Wallen ◽  
P. C. Zee

Recent findings have raised the possibility that some of the age-related changes in the circadian system and the response of the circadian pacemaker to environmental stimuli may involve central serotonergic mechanisms. The present study compared the effects ofpretreatment with the serotonin agonist 8-hydroxy-2(di-n-propylamino)tetralin (5 mg/kg ip) on the magnitude of light-induced phase advances in young (2-4 mo) and old (18-20 mo) golden hamsters. The ability of this serotonin agonist to attenuate the photic phase resetting of circadian locomotor rhythmicity in young animals was decreased by 46% in old hamsters (P < 0.05). These results suggest that deficits in the mechanisms for serotonergic control of circadian function may interfere with the optimal adaptation of the senescent organism to its temporal environment.


2002 ◽  
Vol 282 (5) ◽  
pp. R1382-R1388 ◽  
Author(s):  
Daniel E. Kolker ◽  
Susan Losee Olson ◽  
Jeanette Dutton-Boilek ◽  
Katherine M. Bennett ◽  
Edward P. Wallen ◽  
...  

Aging alters many aspects of circadian rhythmicity, including responsivity to phase-shifting stimuli and the amplitude of the rhythm of melatonin secretion. As melatonin is both an output from and an input to the circadian clock, we hypothesized that the decreased melatonin levels exhibited by old hamsters may adversely impact the circadian system as a whole. We enhanced the diurnal rhythm of melatonin by feeding melatonin to young and old hamsters. Animals of both age groups on the melatonin diet showed larger phase shifts than control-fed animals in response to an injection with the benzodiazepine triazolam at a circadian time known to induce phase advances in the activity rhythm of young animals. Thus melatonin treatment can increase the sensitivity of the circadian timing system of young animals to a nonphotic stimulus, and the ability to increase this sensitivity persists into old age, indicating exogenous melatonin might be useful in reversing at least some age-related changes in circadian clock function.


2000 ◽  
Vol 278 (1) ◽  
pp. R201-R208 ◽  
Author(s):  
M. M. Canal-Corretger ◽  
T. Cambras ◽  
J. Vilaplana ◽  
A. Díez-Noguera

To examine the role of light in the maturation of the circadian pacemaker, twelve groups of rats were raised in different conditions of exposure to constant bright light (LL) during lactation: both duration and timing of LL were varied. We studied the motor activity rhythm of the rats after weaning, first under LL and then under constant darkness (DD). In DD, two light pulses [at circadian time 15 (CT15) and CT22] were applied to test the response of the pacemaker. Greater exposure to LL days during lactation increased the number of rhythmic animals and the amplitude of their motor activity rhythm in the LL stage and decreased the phase delay due to the light pulse at CT15. The timing of LL during lactation affected these variables too. Because the response of the adult to light depended on both the number and timing of LL days during lactation, the exposure to light at early stages may influence the development of the circadian system by modifying it structurally or functionally.


1991 ◽  
Vol 261 (2) ◽  
pp. R491-R495 ◽  
Author(s):  
R. S. Rosenberg ◽  
P. C. Zee ◽  
F. W. Turek

The phase-shifting effects of 1-h light pulses on the circadian rhythm of locomotor activity were measured in young (less than 12 mo old) and old (greater than 16 mo old) hamsters. Phase response curves (PRCs) for both age groups showed an inactive region [approximately circadian time (CT) 0 through CT12], a delay region (CT12 through CT16), and an advance region (CT16 through CT24) as has been reported for young animals. Significant age group differences in the amplitude of phase shifts were measured, with older animals showing larger shifts limited to the region of the "break point" at CT16. The free-running period of the activity rhythm was measured before the first light pulse; age-related decreases of period length consistent with previous reports were measured. The findings indicate that the response of the circadian clock to the major environmental synchronizing agent, light, is different in old hamsters compared with young adults.


1992 ◽  
Vol 263 (4) ◽  
pp. R981-R986 ◽  
Author(s):  
O. Van Reeth ◽  
Y. Zhang ◽  
P. C. Zee ◽  
F. W. Turek

Two different stimuli (i.e., benzodiazepines and dark pulses) inducing phase shifts in the circadian clock of young hamsters through changes in the level of activity do not induce phase shifts in old hamsters, despite the fact that these stimuli induce a similar acute change in locomotor activity in young and old animals. In contrast, old hamsters remain sensitive to the phase-shifting effects of stimuli clearly not associated with any change in locomotor activity (i.e., protein synthesis inhibitors or light). Thus the circadian system of old animals becomes selectively unresponsive to synchronizing signals mediated by the activity-rest state of the animals. Previous age-related changes in circadian rhythmicity that have been observed in mammals, including humans, may be related to a weakened coupling between the activity-rest cycle and the circadian clock.


2009 ◽  
Vol 296 (2) ◽  
pp. R411-R418 ◽  
Author(s):  
Christina L. Ruby ◽  
Rebecca A. Prosser ◽  
Marc A. DePaul ◽  
Randy J. Roberts ◽  
J. David Glass

Disrupted circadian rhythmicity is associated with ethanol (EtOH) abuse, yet little is known about how EtOH affects the mammalian circadian clock of the suprachiasmatic nucleus (SCN). Clock timing is regulated by photic and nonphotic inputs to the SCN involving glutamate release from the retinohypothalamic tract and serotonin (5-HT) from the midbrain raphe, respectively. Our recent in vitro studies in the SCN slice revealed that EtOH blocks photic phase-resetting action of glutamate and enhances the nonphotic phase-resetting action of the 5-HT1A,7 agonist, 8-OH-DPAT. To explore the basis of these effects in the whole animal, we used microdialysis to characterize the pharmacokinetics of intraperitoneal injection of EtOH in the hamster SCN extracellular fluid compartment and then studied the effects of such EtOH treatment on photic and serotonergic phase resetting of the circadian locomotor activity rhythm. Peak EtOH levels (∼50 mM) from a 2 g/kg injection occurred within 20–40 min with a half-life of ∼3 h. EtOH treatment dose-dependently attenuated photic phase advances but had no effect on phase delays and, contrary to in vitro findings, markedly attenuated 8-OH-DPAT-induced phase advances. In a complementary experiment using reverse microdialysis to deliver a timed SCN perfusion of EtOH during a phase-advancing light pulse, the phase advances were blocked, similar to systemic EtOH treatment. These results are evidence that acute EtOH significantly affects photic and nonphotic phase-resetting responses critical to circadian clock regulation. Notably, EtOH inhibition of photic signaling is manifest through direct action in the SCN. Such actions could underlie the disruption of circadian rhythmicity associated with alcohol abuse.


1981 ◽  
Vol 241 (1) ◽  
pp. R62-R66 ◽  
Author(s):  
H. E. Albers

The circadian wheel-running rhythms of gonadectomized adult male, female, and perinatally androgenized female rats, maintained in constant darkness, were examined before and after implantation of Silastic capsules containing cholesterol (C) or estradiol-17 beta (E). The free-running period of the activity rhythm (tau) before capsule implantation tended to be shorter in animals exposed to perinatal androgen. Administration of C did not reliably alter tau in any group. E significantly shortened tau in 100% of females injected with oil on day 3 of life. In females, injected with 3.5 micrograms testosterone propionate on day 3, and males, E shortened or lengthened tau, with the direction and magnitude of this change in tau inversely related to the length of the individual's pretreatment tau. These data indicate that the presence of perinatal androgen does not eliminate the sensitivity of the circadian system of the rat to estrogen, since estrogen alters tau in a manner that depends on its pretreatment length.


2014 ◽  
Vol 53 (5) ◽  
pp. 791-805 ◽  
Author(s):  
Hye Jin Nam ◽  
Kyungjin Boo ◽  
Dongha Kim ◽  
Dong-Hee Han ◽  
Han Kyoung Choe ◽  
...  

2003 ◽  
Vol 285 (5) ◽  
pp. R939-R949 ◽  
Author(s):  
Christopher S. Colwell ◽  
Stephan Michel ◽  
Jason Itri ◽  
Williams Rodriguez ◽  
J. Tam ◽  
...  

The related neuropeptides vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) are expressed at high levels in the neurons of the suprachiasmatic nucleus (SCN), but their function in the regulation of circadian rhythms is unknown. To study the role of these peptides on the circadian system in vivo, a new mouse model was developed in which both VIP and PHI genes were disrupted by homologous recombination. In a light-dark cycle, these mice exhibited diurnal rhythms in activity which were largely indistinguishable from wild-type controls. In constant darkness, the VIP/PHI-deficient mice exhibited pronounced abnormalities in their circadian system. The activity patterns started ∼8 h earlier than predicted by the previous light cycle. In addition, lack of VIP/PHI led to a shortened free-running period and a loss of the coherence and precision of the circadian locomotor activity rhythm. In about one-quarter of VIP/PHI mice examined, the wheel-running rhythm became arrhythmic after several weeks in constant darkness. Another striking example of these deficits is seen in the split-activity patterns expressed by the mutant mice when they were exposed to a skeleton photoperiod. In addition, the VIP/PHI-deficient mice exhibited deficits in the response of their circadian system to light. Electrophysiological analysis indicates that VIP enhances inhibitory synaptic transmission within the SCN of wild-type and VIP/PHI-deficient mice. Together, the observations suggest that VIP/PHI peptides are critically involved in both the generation of circadian oscillations as well as the normal synchronization of these rhythms to light.


1992 ◽  
Vol 263 (5) ◽  
pp. R1099-R1103 ◽  
Author(s):  
P. C. Zee ◽  
R. S. Rosenberg ◽  
F. W. Turek

The phase angle of entrainment of the circadian rhythm of the locomotor activity rhythm to a light-dark (LD) cycle was examined in young (2-5 mo old) and middle-aged (13-16 mo old) hamsters. An age-related phase advance in the onset of locomotor activity relative to lights off was seen during stable entrainment to a 14:10-h LD cycle. In addition, the effects of age on the rate of reentrainment of the circadian rhythm of locomotor activity were examined by subjecting young and middle-aged hamsters to either an 8-h advance or delay shift of the LD cycle. Middle-aged hamsters resynchronized more rapidly after a phase advance of the LD cycle than did young hamsters, whereas young hamsters were able to phase delay more rapidly than middle-aged hamsters. The age-related phase advance of activity onset under entrained conditions, and the alteration of responses in middle-aged hamsters reentraining to a phase-shifted LD cycle, may be due to the shortening of the free-running period of the circadian rhythm of locomotor activity with advancing age that has previously been observed in this species.


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