Reentrainment in Golden Hamsters: Effect of Melatonin,Age and Neonatal Clomipramine Treatment

Golden hamsters (young: 3 month-old; old: more than 12 month-old; or neonatally treated with clomipramine – a serotonin/noradrenaline re-uptake inhibitor antidepressant) were initially entrained to a 14:10 light:dark cycle, and their reentrainment rate after a 6 h phase advance in the photoperiod was determined. Animals took between 6 and 9 days to reentrain. Melatonin (1 mg/kg, i.p.) accelerated reentrainment to the LD cycle in all groups, except for the clomipramine-treated hamsters. These results support an important accelerating effect of the pineal hormone melatonin on resynchronization, no longer observed in clomipramine-treated hamsters.     

Phenotypic differences in reentrainment behavior and sensitivity to nighttime light pulses in siberian hamsters

Spontaneous reentrainment to phase shifts of the photocycle is a fundamental property of all circadian systems. Siberian hamsters are, however, unique in this regard because most fail to reentrain when the LD cycle (16-h light/day) is phase delayed by 5 h. In the present study, the authors compared reentrainment responses in hamsters from 2 colonies. One colony descended from animals trapped in the wild more than 30 years ago (designated "nonentrainers"), and the other colony was outbred as recently as 13 years ago (designated "entrainers"). As reported previously, only 10% of hamsters from the nonentrainer colony reentrained to a 5-h phase delay of the LD cycle. By contrast, 75% of animals from the entrainer colony reentrained to the phase shift. Another goal of this study was to test the hypothesis that failure to reentrain was a consequence of light exposure during the middle of the night on the day of the 5-h phase delay. This hypothesis was tested by exposing animals to 2 h of light during the early, middle, or late part of the night and then subjecting them on the next day to a 3-h phase delay of the photocycle, which is a phase shift to which all hamsters normally reentrain. All animals from both colonies reentrained when light pulses occurred early in the night, but more animals from the entrainer colony, compared to the nonentrainer colony, reentrained when the light pulse occurred in the middle or late part of the night. The phenotypic variation in reentrainment responses is similar to the variation in photoperiodic responsiveness previously reported for these 2 colonies. Phenotypic variation in both traits is due to underlying differences in circadian organization and suggests a common genetic basis for reentrainment responses and photoperiodic responsiveness.     

Melatonin Accelerates Reentrainment After Phase Advance of the Light-dark Cycle in Syrian Hamsters: Antagonism by Flumazenil

The objective of this study was to assess whether melatonin injections accelerated reentrainment of locomotor activity and body temperature rhythms of Syrian hamsters after phase-advancing the light-dark (L:D) cycle and to what extent the effect can be modified by the benzodiazepine (BZP) receptor antagonist flumazenil. After a baseline recording of rhythms, a 6-h phase advance of the L:D cycle was made (day D). Groups of hamsters were subjected, on days D -2, D -1, and D, to one of the following treatments: two injections of vehicle 15 min apart; vehicle followed 15 min later by melatonin (1 mg/kg); flumazenil (5 mg/kg) followed 15 min later by vehicle; or flumazenil (5 mg/kg) followed 15 min later by melatonin (1 mg/kg). Injections were given at the expected time of lights off after the phase shift. In vehicle-injected and untreated controls, ～ 1 day per hour of phase advance was needed to resynchronize the rhythms. The administration of melatonin brought about a significant decrease of resynchronization time to 66% of vehicle-injected controls. The effect of melatonin was prevented by first administering flumazenil. Flumazenil, injected alone, did not modify resynchronization after the shift. The results agree with the view that melatonin activity on circadian rhythmicity is sensitive to central-type BZP antagonism.     

Melatonin Accelerates Reentrainment After Phase Advance of the Light-dark Cycle in Syrian Hamsters: Antagonism by Flumazenil

The objective of this study was to assess whether melatonin injections accelerated reentrainment of locomotor activity and body temperature rhythms of Syrian hamsters after phase-advancing the light-dark (L:D) cycle and to what extent the effect can be modified by the benzodiazepine (BZP) receptor antagonist flumazenil. After a baseline recording of rhythms, a 6-h phase advance of the L:D cycle was made (day D). Groups of hamsters were subjected, on days D -2, D -1, and D, to one of the following treatments: two injections of vehicle 15 min apart; vehicle followed 15 min later by melatonin (1 mg/kg); flumazenil (5 mg/kg) followed 15 min later by vehicle; or flumazenil (5 mg/kg) followed 15 min later by melatonin (1 mg/kg). Injections were given at the expected time of lights off after the phase shift. In vehicle-injected and untreated controls, ∼ 1 day per hour of phase advance was needed to resynchronize the rhythms. The administration of melatonin brought about a significant decrease of resynchronization time to 66% of vehicle-injected controls. The effect of melatonin was prevented by first administering flumazenil. Flumazenil, injected alone, did not modify resynchronization after the shift. The results agree with the view that melatonin activity on circadian rhythmicity is sensitive to central-type BZP antagonism.     

Ovarian hormones influence olfactory cue effects on reentrainment in the diurnal rodent, Octodon degus

Octodon degus, a social hystricomorph rodent, responds to olfactory cues from a gonadally intact female entrained to a light-dark cycle (LD) by accelerating reentrainment of running wheel activity following a 6-h phase advance of the LD cycle. In this study, we examined the role of ovarian hormones in the production of and responsiveness to olfactory social cues in females. Experiment 1: intact females were sequentially phase-advanced 6 h with photic cues alone, or in the presence of an intact female donor, ovariectomized (OVX) donor, a castrated male, or a castrated male with testosterone replacement. Acceleration of reentrainment occurred only in the presence of the intact female donor while reentrainment was delayed by OVX donors. Experiment 2: OVX females undergoing a 6-h phase advance did not accelerate reentrainment in the presence of an intact female donor compared to reentrainment with photic cues alone. Thus, ovarian hormones are necessary for both the production of and responsiveness to olfactory cues. Experiment 3: OVX females implanted with estrogen-filled Silastic capsules did not accelerate reentrainment following the 6-h phase advance in the presence of an intact donor, whereas animals implanted with a combination of estrogen- and progesterone-filled capsules (Experiment 4) reduced the length of time needed to reentrain in the presence of an intact donor. Therefore, combined progesterone and estrogen are sufficient for responsiveness to the effective olfactory cue in intact donor females. These data clarify that the sex difference in sensitivity to non-photic odor effects on circadian reentrainment is caused by both the testosterone's inhibitory effects (Octodon degus. J. Biol. Rhythms 18 (2003) 43-50) and the enhancing effects of progesterone and estrogen.     

Constant darkness restores entrainment to phase-delayed Siberian hamsters

Over 90% of Siberian hamsters (Phodopus sungorus) fail to reentrain to a 5-h phase delay of a 16:8-h photocycle. Because constant darkness (DD) restores rhythms disrupted by constant light, we tested whether DD could also restore entrainment. DD began 0, 5, or 14 days after a 5-h phase delay, and the light-dark cycle was reinstated 14 days later. All hamsters exposed to DD on day 0 reentrained, whereas 42% reentrained irrespective of whether DD began 5 or 14 days later. For these latter two groups, tau (tau) and alpha (alpha) in DD predicted reentrainment; animals that reentrained had a mean tau and alpha of 24.1 and 8.9 h, respectively, whereas those that failed to reentrain maintained a mean tau and alpha of 25.0 and of 7.1 h, respectively. Restoration of entrainment by DD is somewhat paradoxical because it suggests that reentrainment to the photocycle was prevented by continued exposure to that same photocycle. The dichotomy of circadian responses to DD suggests "entrainment" phenotypes that are similar to those of photoperiodic responders and nonresponders.     

The Endogenous Melatonin (MT) Signal Facilitates Reentrainment of the Circadian System to Light-Induced Phase Advances by Acting Upon MT2 Receptors

The indolamine melatonin is an important rhythmic endocrine signal in the circadian system. Exogenous melatonin can entrain circadian rhythms in physiology and behavior, but the role of endogenous melatonin and the two membrane-bound melatonin receptor types, MT1 and MT2, in reentrainment of daily rhythms to light-induced phase shifts is not understood. The present study analyzed locomotor activity rhythms and clock protein levels in the suprachiasmatic nuclei (SCN) of melatonin-deficient (C57BL/6J) and melatonin-proficient (C3H/HeN) mice, as well as in melatonin-proficient (C3H/HeN) mice with targeted deletion of the MT1, MT2, or both receptors, to determine effects associated with phase delays or phase advances of the light/dark (LD) cycle. In all mouse strains and genotypes, reentrainment of locomotor activity rhythms was significantly faster after a 6-h phase delay than a 6-h phase advance. Reentrainment after the phase advance was, however, significantly slower than in melatonin-deficient animals and in mice lacking functional MT2 receptors than melatonin-proficient animals with intact MT2 receptors. To investigate whether these behavioral differences coincide with differences in reentrainment of clock protein levels in the SCN, mPER1, mCRY1 immunoreactions were compared between control mice kept under the original LD cycle and killed at zeitgeber time 04 (ZT04) or at ZT10, respectively, and experimental mice subjected to a 6-h phase advance of the LD cycle and sacrificed at ZT10 on the third day after phase advance. This ZT corresponds to ZT04 of the original LD cycle. Under the original LD cycle, the numbers of mPER1- and mCRY1-immunoreactive cell nuclei were low at ZT04 and high at ZT10 in the SCN of all mouse strains and genotypes investigated. Notably, mouse strains with intact melatonin signaling and functional MT2 receptors showed a significant increase in the number of mPER1- and mCRY1-immunoreactive cell nuclei at the new ZT10 as compared to the former ZT04. These data suggest the endogenous melatonin signal facilitates reentrainment of the circadian system to phase advances on the level of the SCN molecular clockwork by acting upon MT2 receptors. (Author correspondence: M.Pfeffer@em.uni-frankfurt.de)     

Timely administration of melatonin accelerates reentrainment to phase-shifted light-dark cycles in the field mouse Mus booduga

The effect of melatonin on the rate of reentrainment after a 6h phase delay and a 6h phase advance in the light-dark (LD) cycle was assayed in the nocturnal field mouse Mus booduga. After a phase delay of 6h in the LD cycle, a single dose of melatonin (1 mg/kg) was administered for three consecutive days at about CT4 (circadian time 4). After a phase advance of 6h in the LD cycle, melatonin was administered for three consecutive days at about CT22. Melatonin was found to accelerate reentrainment in both cases. Melatonin-treated animals took significantly fewer cycles to reentrain compared to vehicle-treated (50% dimethylsulfoxide [DMSO]) and nontreated control animals.     

The endogenous melatonin (MT) signal facilitates reentrainment of the circadian system to light-induced phase advances by acting upon MT2 receptors

The indolamine melatonin is an important rhythmic endocrine signal in the circadian system. Exogenous melatonin can entrain circadian rhythms in physiology and behavior, but the role of endogenous melatonin and the two membrane-bound melatonin receptor types, MT1 and MT2, in reentrainment of daily rhythms to light-induced phase shifts is not understood. The present study analyzed locomotor activity rhythms and clock protein levels in the suprachiasmatic nuclei (SCN) of melatonin-deficient (C57BL/6J) and melatonin-proficient (C3H/HeN) mice, as well as in melatonin-proficient (C3H/HeN) mice with targeted deletion of the MT1, MT2, or both receptors, to determine effects associated with phase delays or phase advances of the light/dark (LD) cycle. In all mouse strains and genotypes, reentrainment of locomotor activity rhythms was significantly faster after a 6-h phase delay than a 6-h phase advance. Reentrainment after the phase advance was, however, significantly slower than in melatonin-deficient animals and in mice lacking functional MT2 receptors than melatonin-proficient animals with intact MT2 receptors. To investigate whether these behavioral differences coincide with differences in reentrainment of clock protein levels in the SCN, mPER1, mCRY1 immunoreactions were compared between control mice kept under the original LD cycle and killed at zeitgeber time 04 (ZT04) or at ZT10, respectively, and experimental mice subjected to a 6-h phase advance of the LD cycle and sacrificed at ZT10 on the third day after phase advance. This ZT corresponds to ZT04 of the original LD cycle. Under the original LD cycle, the numbers of mPER1- and mCRY1-immunoreactive cell nuclei were low at ZT04 and high at ZT10 in the SCN of all mouse strains and genotypes investigated. Notably, mouse strains with intact melatonin signaling and functional MT2 receptors showed a significant increase in the number of mPER1- and mCRY1-immunoreactive cell nuclei at the new ZT10 as compared to the former ZT04. These data suggest the endogenous melatonin signal facilitates reentrainment of the circadian system to phase advances on the level of the SCN molecular clockwork by acting upon MT2 receptors.     

Restraint stress delays reentrainment in male and female diurnal and nocturnal rodents

A temporary loss of normal circadian entrainment, such as that associated with shift work and transmeridian travel, can result in an array of detrimental symptoms, making rapid reentrainment of rhythmicity essential. While there is a wealth of literature examining the effects of stress on the entrained circadian system, less is known about the influence of stress on circadian function following a phase shift of the light: dark (LD) cycle. The authors find that recovery of locomotor activity synchronization is altered by restraint stress in the diurnal rodent Octodon degus (degu) and the nocturnal rat. In the first experiment, degus were subjected to a 6-h phase advance of the LD cycle. Sixty minutes after the new lights-on, animals underwent 60 min of restraint stress. The number of days it took each animal to reentrain its activity rhythms to the new LD cycle was recorded and compared to the number of days it took the animal to reentrain under control conditions. When subjected to restraint stress, degus took 30% longer to reentrain their activity rhythms (p < 0.01). In a second experiment, rats underwent a similar experimental paradigm. As with the degus, stress significantly delayed the reentrainment of rats' activity rhythms (p < 0.01). There was no interaction between sex and stress on the rate of reentrainment for either rats or degus. Furthermore, there was no effect of stress on the free-running activity rhythm of degus, suggesting that the effect of stress on reentrainment rate is not secondary to alterations of period length. Together, these data point to a detrimental effect of stress on recovery of entrainment of circadian rhythms, which is independent of activity niche and sex.     

Light pulses do not induce c-fos or per1 in the SCN of hamsters that fail to reentrain to the photocycle

Circadian activity rhythms of most Siberian hamsters (Phodopus sungorus sungorus) fail to reentrain to a 5-h phase shift of the light-dark (LD) cycle. Instead, their rhythms free-run at periods close to 25 h despite the continued presence of the LD cycle. This lack of behavioral reentrainment necessarily means that molecular oscillators in the master circadian pacemaker, the SCN, were unable to reentrain as well. The authors tested the hypothesis that a phase shift of the LD cycle rendered the SCN incapable of responding to photic input. Animals were exposed to a 5-h phase delay of the photocycle, and activity rhythms were monitored until a lack of reentrainment was confirmed. Hamsters were then housed in constant darkness for 24 h and administered a 30-min light pulse 2 circadian hours after activity onset. Brains were then removed, and tissue sections containing the SCN were processed for in situ hybridization. Sections were probed with Siberian hamster c-fos and per1 mRNA probes because light rapidly induces these 2 genes in the SCN during subjective night but not at other circadian phases. Light pulses induced robust expression of both genes in all animals that reentrained to the LD cycle, but no expression was observed in any animal that failed to reentrain. None of the animals exhibited an intermediate response. This finding is the first report of acute shift in a photocycle eliminating photosensitivity in the SCN and suggests that a specific pattern of light exposure may desensitize the SCN to subsequent photic input.     

Siberian hamsters that fail to reentrain to the photocycle have suppressed melatonin levels

Siberian hamsters readily reentrain to a 3-h phase delay of the photocycle (16 h light/day) but fail to reentrain to a 5-h phase delay. This study tested whether melatonin production was suppressed in animals that failed to reentrain. Melatonin was measured on the day before, day of, or several days after each phase shift. Melatonin levels measured 4 h after dark onset were approximately 83 microg/ml on the day before each phase delay and undetectable (<6 microg/ml) during the light phase on the day of the phase shift. Activity onsets regained their prior phase relationship to the photocycle 4 (3 h) or 5 (5 h) days after the phase shift; on that day, melatonin levels were measured 4 h after dark onset. Melatonin levels were unaffected by the 3-h phase delay (>57.6 microg/ml) but were undetectable after a 5-h phase delay (<8 microg/ml). Thus melatonin remained suppressed only after the phase delay to which hamsters also fail to reentrain. This relationship suggests that the propensity for reentrainment may be influenced by changes in melatonin production following a phase shift of the photocycle.     

Reentrainment of the circadian pacemaker through three distinct stages

Circadian rhythms are endogenously generated by a central pacemaker and are synchronized to the environmental LD cycle. The rhythms can be resynchronized, or reentrained, after a shift of the LD cycle, as in traveling across time zones. The authors have performed high-resolution mapping of the pacemaker to analyze the reentrainment process using rat pineal melatonin onset (MT(on)) and melatonin offset (MT(off)) rhythms as markers. Following LD (12:12) delays of 3, 6, and 12 h, MT(on) was phase locked immediately, whereas MT(off) shifted rapidly during the initial 1 through 3 cycles. In all animals, the MT(off) shifted beyond their expected phase positions in the new LD cycle, which resulted in a transient expansion of melatonin secretion duration for several cycles. It took MT(off) only 1, 2, or 3 cycles to complete most of the required phase shifts after 3, 6, or 12 h of the LD cycle delays, respectively. However, the final stabilization of phase relationships of both MT(on) and MT(off) required at least 6 cycles for rats experiencing a 3-h LD delay and much longer for the rest. These results reaffirmed the notion that both onset and offset phases of melatonin rhythms are important markers for the pacemaker and demonstrated that the reentrainment of the central pacemaker to a delay shift of the LD cycle is a 3-step process: an immediate phase lock of onset and a rapid delay shift of offset rhythms, overshoot of the offset, and, finally, a slow adjustment of both onset and offset phases. This study represents the 1st detailed analysis of the pacemaker behavior during reentrainment using melatonin and supports the notion that the eventual adaptation of the circadian pacemaker to a new time zone is a time-consuming process.     

Odor-specific effects on reentrainment following phase advances in the diurnal rodent, Octodon degus

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.     

Use of benzodiazepines to manipulate the circadian clock regulating behavioral and endocrine rhythms

Extensive studies have now been carried out demonstrating that the systemic administration of the short-acting benzodiazepine, triazolam, can have pronounced effects on both behavioral and endocrine circadian rhythms. For example, three daily injections of triazolam can phase-advance the circadian rhythm of pituitary luteinizing hormone release and locomotor activity by about 2-3 h in female hamsters maintained in constant light. Triazolam has also been found to facilitate the rate of reentrainment of the activity rhythm following an 8-hour advance or delay in the light-dark cycle. Limited studies with other short-acting benzodiazepines indicate that the effects of triazolam on the circadian system of hamsters can be generalized to this class of drugs. Recent studies in humans indicate that treatment with triazolam can alter the time it takes for human endocrine rhythms to become reentrained following an 8-hour delay in the sleep-wake and light-dark cycle. Such findings raise the possibility that short-acting benzodiazepines may prove useful in reducing the symptoms associated with 'jet-lag' and rotating shift-work schedules as well as in the treatment of various physical and mental illnesses that have been associated with a disorder of biological timekeeping.     

Modeling interactions between photic and nonphotic entrainment mechanisms in transmeridian flights

In transmeridian flights, photic and nonphotic entrainment mechanisms are expected to interact dynamically in the human circadian system. In order to simulate the reentrainment process of the circadian rhythms, the photic entrainment mechanism was introduced to our previous model, which consisted of three coupled oscillators. Regardless of flight direction, a large time difference beyond 10 h tended to induce the antidromic reentrainment. The partition between the oscillators resulted for the eastward flight over a 10-h or longer time difference and the westward over 6 h or longer. The simulated reentrainment processes almost coincided with empirical knowledge. Simulated effects of physical exercise showed that some antidromic reentrainments were switched to the orthodromic ones for the eastward flight and most of the partitions between the oscillators were prevented in the westward flight. These results are due to an augmentation of the entrainment pressure of the rest–activity cycle on the oscillators. The mechanisms underlying these various reentrainment patterns were explained based on the photic response, the interactions between the oscillators, and their adaptive modification. The simulation results suggest that an appropriate selection of departure time and physical exercise could ease the jet lag caused by transmeridian flight.This research was supported by a Grant-In-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Nos. 14015205, 15014204, and 15560372).     

Inhibiting cortisol response accelerates recovery from a photic phase shift

Jetlag results when a temporary loss of circadian entrainment alters phase relationships among internal rhythms and between an organism and the outside world. After a large shift in the light-dark (LD) cycle, rapid recovery of entrainment minimizes the negative effects of internal circadian disorganization. There is evidence in the existing literature for an activation of the hypothalamic-pituitary-adrenal (HPA) axis after a photic phase shift, and it is possible that the degree of HPA-axis response is a determining factor of reentrainment time. This study utilized a diurnal rodent, Octodon degus, to test the prediction that the alteration of cortisol levels would affect the reentrainment rate of circadian locomotor rhythms. In experiment 1, we examined the effects of decreased cortisol (using metyrapone, an 11beta-hydroxylase inhibitor) on the rate of running-wheel rhythm recovery after a 6-h photic phase advance. Metyrapone treatment significantly shortened the length of time it took animals to entrain to the new LD cycle (11.5% acceleration). In experiment 2, we examined the effects of increased cortisol on the rate of reentrainment after a 6-h photic phase advance. Increasing plasma cortisol levels increased the number of days (8%) animals took to reentrain running-wheel activity rhythms, but this effect did not reach significance. A third experiment replicated the results of experiment 1 and also demonstrated that suppression of HPA activity via dexamethasone injection is capable of accelerating reentrainment rates by approximately 33%. These studies provide support for an interaction between the stress axis and circadian rhythms in determining the rate of recovery from a phase shift of the LD cycle.     

Social Cues Accelerate Reentrainment of Circadian Rhythms in Diurnal Female Octodon Degus (Rodentia-Octodontidae)

Previous studies paired diurnal Octodon degus undergoing/phase advances (phase-shifters) with those entrained to a light-dark (LD) cycle (donors). Results included opposite outcomes of male and female social cues on resynchronization following 6-h advances in females, but no effect of social cues on male resynchronization. The first experiment determined if social cues could influence resynchronization rates of circadian rhythms in male and female degus following a 6-h phase delay of the LD cycle. Female phase-shifters resynchronized temperature and activity rhythms 20–35% faster when housed with either entrained (donor) females or males compared with females housed alone. No significant differences in resynchronization rate for phase-shifting males existed between test conditions. This experiment extends the previous finding that females, but not males, respond strongly to donor cues to increase resynchronization rates in the presence of light. A second experiment determined that accelerated resynchronization rates of female phase-shifters housed with female donors were due to social cues directly affecting the circadian system rather than the result of social masking. On the day following resynchronization with or without a female donor present, phaseshifters were transferred individually to constant conditions (DD). The temperature and activity rhythms of female phase-shifters free-ran from the point at which resynchronization occurred for both the control and experimental females. Thus, social cues accelerate true reentrainment, not masking, of the circadian system in the presence of a LD cycle in female degus. Donor cues from females enhance reentrainment after advances and delays, but the effect of male donor cues is dependent on the direction of the phase shift.     

Vitamin B12 accelerates re-entrainment of activity rhythms in rats.

The effects of methyl vitamin B12 (5-6 mg/kg, p.o.) on the entrainment of circadian running wheel activity rhythm to a new lighting schedule were measured in rats. After the light-dark (LD) cycle was abruptly reversed, rats given vitamin B12 took less time to entrain their circadian locomotor activity rhythm to the new cycle than did controls. This result indicates that vitamin B12 accelerates the reentrainment of the mammalian circadian activity rhythm following an abrupt change in the environmental LD cycle.     

Melatonin accelerates reentrainment of the circadian rhythm of its own production after an 8-h advance of the light-dark cycle

Summary The rhythm in melatonin production in the rat is driven by a circadian rhythm in the pineal N-acetyltransferase (NAT) activity. Rats adapted to an artificial lighting regime of 12 h of light and 12 h of darkness per day were exposed to an 8-h advance of the light-dark regime accomplished by the shortening of one dark period; the effect of melatonin, triazolam and fluoxetine, together with 5-hydroxytryptophan, on the reentrainment of the NAT rhythm was studied.In control rats, the NAT rhythm was abolished during the first 3 cycles following the advance shift. It reappeared during the 4th cycle; however, the phase relationship between the evening rise in activity and the morning decline was still compressed.Melatonin accelerated the NAT rhythm reentrainment. In rats treated chronically with melatonin at the new dark onset, the rhythm had already reappeared during the 3rd cycle, in the middle of the advanced night, and during the 4th cycle, the phase relationship between the evening onset and the morning decline of the NAT activity was the same as before the advance shift. In rats treated chronically with melatonin at the old dark onset or in those treated with melatonin 8 h, 5 h and 2 h after the new dark onset during the 1st, 2nd and 3rd cycle, respectively, following the advance shift, the NAT rhythm reappeared during the 3rd cycle as well but in the last third of the advanced night only.Neither triazolam nor fluoxetine together with 5-hydroxytryptophan administered around the new dark onset facilitated NAT rhythm reentrainment after the 8-h advance of the light-dark cycle.Abbreviations NAT N-acetyltransferase - LD cycle light-dark cycle - CT circadian time - LD xy light dark cycle comprising x h of light and y h of darkness