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Objective: Circadian rhythms are present almost in all living organisms and synchronized with the zeitgebers (time givers), especially lightdark (LD) cycles. The jetlag and rotating shift work schedules lead to desynchronization of the circadian clock with zeitgebers which may cause various health problems. Studies have shown that withanolide-A (WA) is a potent nootropic and neuroprotective agent found in Withania somnifera. Thus, the objective was to study the effect of WA on the circadian locomotor activity rhythm following the phase inversion of 12:12 h LD cycle in mice and its impact on the spatial memory in mice.Methods: Adult male mice were housed in the chronocubicle and recorded circadian locomotor activity rhythm by using ClockLab setup. The experimental mice were administered with WA (10 μmol/kg/day) for 13 consecutive days at about ZT15 and then evoked an acute phase inversion of 12:12 h light-dark cycle. Further, the Barnes maze test was performed to check the effect of WA on spatial memory following the phase inversion.Results: The results showed that WA-treated group took significantly fewer transient cycles (4.66+0.66) for re-entrainment than the control (9.5+0.43) and vehicle-treated (8.33+1.28) mice following the phase inversion. Similarly, WA-treated mice traveled less distance to reach the target zone in the Barnes maze compared to vehicle and control groups.Conclusion: These results suggest that the WA may act as chronobiotic and neuroprotective agent since it decreased the transient cycles for re-entrainment and retaining spatial memory following the phase inversion.

The circadian system maintains internal 24 h oscillation of behavior and physiology, and its misalignment with external light-dark (LD) cycle results in negative health outcomes. In order to elucidate the effect of prolonged constant condition and the differences in the response between nocturnal and diurnal species, we studied the effects of constant light (LL) and constant darkness (DD) on a diurnal (squirrel) and a nocturnal (mouse) rodent species, focusing on the endocrine, inflammatory and antioxidant systems associated with depression-like behavior. Squirrels and mice (n = 10/group) were placed in chronocubicle under 12:12 h LD cycle, LL and DD. After 4 weeks, animals were subjected to sucrose preference test and blood and brain tissues were collected for measuring melatonin, corticosterone, proinflammatory cytokine, tumor necrosis factor-α (TNF-α) and the activity of primary antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD). The results show that in diurnal squirrels, prolonged constant darkness reduced sucrose preference, CAT, and SOD, increased corticosterone and TNF-α levels, but caused no significant change in the melatonin compared to LD condition. In contrast, in nocturnal mice constant darkness caused no significant changes in sucrose preference and corticosterone levels, increased melatonin, CAT and SOD levels but decreased TNF-α levels. Chronic LL caused a similar response in both squirrels and mice: it decreased sucrose preference, melatonin, CAT and SOD levels but increased corticosterone and TNF-α levels. Together, the study demonstrates differential effects of altered light-dark cycle in a diurnal and a nocturnal rodent on interrelated endocrine, inflammatory and antioxidant systems associated with depression-like behavior, with constant light having adverse effects on both species but constant darkness having a negative effect mainly in the diurnal squirrels.

Social cues are potent non-photic modulators of the circadian clock and play a vital role in resetting the endogenous clock. Several lines of evidence strongly suggest a functional link between olfactory cues and the circadian clock. However, there is a paucity of information on the effects of social interaction with the conspecifics of the opposite sex on the circadian clock. Hence, we studied the effect of social cues of sexually mature naive opposite sex of the conspecific on the phase resetting of the circadian clock at various circadian times (CT) and molecular changes at the suprachiasmatic nuclei (SCN) and odor responsive structure in the brain of mice. Sexually naive adult male and female free-running mice (designated as 'runners') were exposed to the conspecifics of the opposite-sex ('strangers') for 30 min at CT3, CT9, CT15, and CT21. Both male and female 'runners' exhibited a phase advance at CT3, delay at CT21, and no response at CT9. However, at CT15 only the male 'runners' exhibited phase advance but not the female 'runners'. Control mice did not elicit any significant phase shifts at all CTs. Social interactions with conspecifics of the opposite-sex up-regulated c-fos/C-FOS, omp in the olfactory bulb, per-1/PER-1 in the SCN, C-FOS, and PER-1 in the piriform cortex of both male and female runners at CT3. However, at CT15 up-regulation of variables only occurred in male but not in female runners. Together, the present investigation has shown the gender difference in circadian clock responses for social cues with conspecific of the opposite-sex in mice.

Fil: Soni, Sanjeev Kumar. Banaras Hindu University. Institute of Sciences. Department of Zoology. Chronobiology Laboratory; India Fil: Basu, Priyoneel. Banaras Hindu University. Institute of Sciences. Department of Zoology. Chronobiology Laboratory; India Fil: Singaravel, Muniyandi. Banaras Hindu University. Institute of Sciences. Department of Zoology. Chronobiology Laboratory; India Fil: Sharma, Ramaswamy. UT Health San Antonio. Department of Cell Systems and Anatomy; Estados Unidos Fil: Pandi Perumal, Seithikurippu R. Somnogen Canada; Canadá Fil: Cardinali, Daniel Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Abstract: Chronic disruption of circadian rhythms which include intricate molecular transcription-translation feedback loops of evolutionarily conserved clock genes has serious health consequences and negatively affects cardiovascular physiology. Sirtuins (SIRTs) are nuclear, cytoplasmic and mitochondrial histone deacetylases that influence the circadian clock with clock-controlled oscillatory protein, NAMPT, and its metabolite NAD+. Sirtuins are linked to the multi-organ protective role of melatonin, particularly in acute kidney injury and in cardiovascular diseases, where melatonin, via upregulation of SIRT1 expression, inhibits the apoptotic pathway. This review focuses on SIRT1, an NAD+-dependent class III histone deacetylase which counterbalances the intrinsic histone acetyltransferase activity of one of the clock genes, CLOCK. SIRT1 is involved in the development of cardiomyocytes, regulation of voltage-gated cardiac sodium ion channels via deacetylation, prevention of atherosclerotic plaque formation in the cardiovascular system, protection against oxidative damage and anti-thrombotic actions. Overall, SIRT1 has a see-saw effect on cardioprotection, with low levels being cardioprotective and higher levels leading to cardiac hypertrophy.

Several studies have reported activity patterns of various diurnal species from the order Rodentia, in which most of the species are nocturnal. Most of these studies have been performed under contr...

Melatonin, an essential pineal hormone, acts as a marker of the circadian clock that regulates biological rhythms in animals. The effects of exogenous melatonin on the circadian system of nocturnal...

The hippocampus, an extension of the temporal part of the cerebral cortex, plays a crucial role in learning and memory. Structural and functional complexity within the hippocampus is greatly affected by a variety of external environmental stimuli including alteration in the light-dark (LD) cycle. The effect of altered LD cycle in learning and memory associated cognitive impairment has been reported in rodents. However, a comparative study of underlying neuronal changes between nocturnal and diurnal species is not well explored. The objective of the present study was to explore the morphological changes in hippocampal CA1 and DG neurons in response to prolonged constant condition

Chronic jet lag has deleterious effects on many physiological parameters. Most simulations of chronic jet lag consist of repeated advances only, while real-life conditions may differ. We compared n...

Chronic disruption of circadian rhythms which include intricate molecular transcription-translation feedback loops of evolutionarily conserved clock genes has serious health consequences and negatively affects cardiovascular physiology. Sirtuins (SIRTs) are nuclear, cytoplasmic and mitochondrial histone deacetylases that influence the circadian clock with clock-controlled oscillatory protein, NAMPT, and its metabolite NAD

Risperidone is an atypical antipsychotic that is active at multiple dopamine and serotonin receptor subtypes. Based on its high affinity for serotonin receptors, we predicted that it might reset circadian rhythms in a nocturnal rodent. We report temporally differentiated and differential effects of various doses of risperidone on the voluntary locomotor activity rhythm in the Indian field mice, Mus booduga. Risperidone (0.5 mg/kg) elicited phase delays at phases between CT (circadian time) 12 to CT18 and CT0 to CT3, and phase advances at CT6, CT9 and CT21. However, mice injected at CT6 showed maximum advances (1.299 ± 0.286 h), whereas at CT15 showed maximum delays (−1.514 ± 0.312 h). Increasing the dose beyond 0.5 mg/kg at maximally responsive CTs (CT6 and CT15) resulted in progressively smaller but significant shifts. Thus, 0.5 mg/kg is the optimal dose in this species. The fact that risperidone resets the circadian rhythm in a mammal can be extended to clinical studies and used for optimal adju...

Human chronotypes (differences in preference for early or late rising each day) have been extensively studied in recent years, but no attempt has been made to compare human chronotypes with the chronotypes of other animal species. We evaluated behavioral chronotypes in 16 mammalian species along a body size gradient of five orders of magnitude (from mice to cattle). Individuals of all species were studied under a 12L:12D photoperiod in a thermoneutral environment with food and water available at all times. Rhythms of locomotor activity were analyzed for onset time, acrophase, and robustness. Neither of these rhythmic parameters was significantly related to body size, but onset time and acrophase varied considerably from species to species, thus characterizing diurnal and nocturnal species. Chronotype spreads ranged from less than an hour in sheep to almost 24h in cats, thus extending both below and above the human chronotype spread of 6h. The variability of chronotype (as quantified by the standard deviation of group means) was much larger between species than within species and also larger between individuals of a species than within individuals on consecutive days. These results help situate the matter of human chronotypes within the broader context of variability in the phase angle of entrainment of circadian rhythms in animals.

Circadian rhythms control many facets of biology and their disruption can be associated with severe pathological conditions. In healthy individuals, disturbances to the sleep-wake cycle can be the root cause of many problems. In the present review, we explore the major factors contributing to circadian rhythm disruption, including sleep disorders, jet lag, and shift work. The consequences of these disruptions on central and peripheral clocks and the important areas of the body controlled by them involve immune function and metabolism, as well as alterations in cognitive abilities, thereby impairing social and occupational behavior. Further work exploring clock genes, light exposure, and cellular changes will be critical for identifying how these factors interact to affect health and behavior.

Fisetin, a bioactive flavonoid, found in many fruits, was administered orally (50 mg/kg body weight) to hyperammonemic rats (treated with ammonium chloride (AC) for 8 weeks (i.p. injections, 100 mg/kg body weight). Treatment with AC augmented oxidative stress, levels of ammonia, enzymes (alanine and aspartate transaminases and alkaline phosphatase) in blood, glutamate and glutamine content in brain, caused disturbances in the circadian locomotor rhythm with a reduction in amplitude and period and downregulated the expression of soluble guanylyl cyclase (sGC) and glial fibrillary acidic protein (GFAP) in brain. Co-treatment of fisetin treatment with AC, prevented the AC-induced elevation in oxidative stress, normalized the levels of ammonia, transaminases and alkaline phosphatase in circulation, glutamate and glutamine in brain, upregulated the expression of sGC and GFAP and stabilized the circadian locomotor rhythm. Thus, fisetin assuages AC induced effects through its antioxidant, anti-inflammatory, cytoprotective, neuroprotective and neurotrophic properties.

We quantified motor learning during voluntary wheel-running activity in the Indian pygmy field mouse, Mus terricolor. Wheel running in naive adults was monitored using the Clocklab system. A group of mice having 15 days prior wheel-running experience served as the control. The daily maximum wheel activity for the naive group increased from 21 ± 7 counts/min to 62 ± 4 counts/min in 15 days. The experienced group exhibited 62 ± 1 counts/min throughout the experiment. A significant correlation between days of wheel running and natural log of the highest count/min existed in the experimental group, but not in the experienced group. Thus, improvement in wheel running follows a logarithmic learning curve. Several research applications for this quantification have been discussed. The most important outcome of this quantification is that it primes the mice for a study in which the retention period for this motor learning, i.e. the time taken to “forget” motor learning during wheel running will be elucidated.

L-5-Hydroxytryptophan (5-HTP), the precursor of serotonin, is known to cause temporally differentiated phase shifts. However, its effects on acceleration of re-entrainment have not been demonstrated before. We report significant acceleration of re-entrainment to a 6-h advanced light dark schedule by 50 mg/kg 5-HTP (∼8 transients reduced to ∼3 transients) injected at ∼ZT 6 in the nocturnal Indian pygmy field mouse, Mus terricolor. The mechanistic explanation is currently unknown, but this probably occurs through serotonergic phase and period modifications. 5-HTP is thus potentially useful as a chronobiotic in circadian rhythm disorders.

L-5-Hydroxytryptophan (5-HTP), the precursor of serotonin, has phase-resetting ability under constant conditions in mammals. However, it is not known whether it can entrain a free-running rhythm. We report that 5-HTP (50 mg/kg) entrains the free-running rhythm of Mus terricolor to 24 h, when presented once in 24 h at zeitgeber time (ZT) 6, corresponding to its previously known circadian time (CT) of maximum advance in complete darkness (CT 6), on the last pre-intervention day. This entrainment is accompanied by shortening of the period and visible after withdrawal of injections. After-effects may persist for a few days. The mechanistic explanation is currently unknown, but this probably occurs through serotonergic phase and period modifications. 5-HTP is thus potentially useful as a chronobiotic in circadian rhythm disorders.

We report the presence of variations in the rate and direction of re-entrainment to acute simulated jet lag in wild-caught North Indian palm squirrels (Funambulus pennanti). Adult laboratory and wheel-acclimated (Lafayette, USA) males (N = 30) were entrained to a 12:12 h light/dark (LD) schedule, followed by a 9 h advance of the LD schedule to simulate acute jet lag. The direction and rate of re-entrainment, i.e. the number of orthodromic (advancing) and antidromic (delaying) transients, the acrophases of daily rhythms in each case, duration of activity (α) and phase angle relationship (ψ) were noted using Clocklab (Coulbourn, USA). The squirrels exhibited distinct variations in their response to simulated acute jet lag, re-entraining either slowly (14/30) or rapidly (10/30) by advancing transients, or undergoing antidromic re-entrainment slowly (5/30), and, in only one individual, rapidly. Acrophases re-entrained slower than onsets. α underwent compression during re-entrainment, particularly during fast ...

We report some basic circadian characteristics in Mus terricolor, the nocturnal pygmy field mouse. Both male and female M. terricolor entrain well to a 12:12 light:dark schedule. Activity is completely nocturnal in distribution in LD. ρ and α in LD differ significantly between males and females. Free-running circadian locomotor activity rhythm in DD was 23.69 h (males) and 23.46 h (females). In LD, ψ was −0.20 h and −0.15 h in males and females, respectively. Rhythms were accurate (6.02 in males/7.30 in females [h−1]) and precise (4.83 in males /4.74 in females [h−1]). Fifteen-minute perturbations with ∼70 lux white light in DD led to predictable phase advances and delays. Mus terricolor took ∼7 days to re-entrain to a 6 h advance in the ambient light schedule, with rapid resynchronization to a 6 h phase delay. These results indicate that M. terricolor is a good model animal for in-depth research in circadian biology.

Serotonergic agents usually attenuate light-induced phase shifts in nocturnal species. L-5-Hydroytrytptophan (5-HTP) is a non-specific serotonergic agonist and the natural precursor of serotonin. We investigated the ability of 5-HTP to potentiate or attenuate light-induced phase shifts using a comparatively lower intensity of light (∼70 lux). Mice free-running in DD were given either light exposure at circadian times (CTs) 15 and 21 with saline (light-exposed control) or 50 mg/kg of 5-HTP (Himedia) at 0.5 circadian h prior to light exposure. L-5-Hydroytrytptophan potentiated the phase advance of the rhythm caused by light at CT 21; however, 5-HTP fails to significantly attenuate/potentiate phase delays. Total activity increased during phase advance potentiation, compared to control, indicating that this phenomenon may possibly be at least partially behavioral arousal-dependent. These preliminary findings are interesting and unexpected; further experimentation is necessary, and the results indicate possibl...

Biological rhythms are ubiquitous phenomena that enable an organism to temporally adapt to the environment. Jet lag occurs during rapid transmeridial transport and disrupts the normal biological rhythm. Disruption of the biological rhythm is known to reduce survival and hasten tumorigenesis in male mice. Dalton's lymphoma (DL) is a spontaneous and highly invasive T-cell lymphoma that develops as an ascitic tumor in murines. DL was induced by serial implantation of live ascite cells in laboratory-acclimated age-matched male and female AKR mice. The mice were then subjected to simulated chronic jet lag (CJL) by rapidly and alternately advancing and delaying the ambient light dark cycle by 8 h every 2 days. Females, but not males, with DL became arrhythmic after exposure to simulated CJL. Survival was significantly curtailed in both male and female mice with DL + CJL compared to survival in mice with DL alone or CJL alone (∼16 days after DL induction in mice and facing jet lag, and ∼28 days after DL inductio...

Dalton's lymphoma (DL) is a spontaneous and highly invasive T-cell lymphoma that develops as an ascitic tumor in murines. DL was induced by serial implantation of live ascite cells in laboratory-acclimated age-matched male AKR mice. The effects of DL on the locomotor activity rhythm were studied under 12:12 h light:dark (LD) cycle. A significant decrease in the total and peak wheel-running activity was seen after the induction of DL, in comparison with the vehicle-injected control group. Durations of activity and rest were altered in DL mice, with a sharp daily increase in the duration of rest in the DL group. Circadian time period and acrophase of the rhythm remained similar in both control and DL mice. The mean estimate of statistic of rhythmicity (MESOR) and the amplitude of the locomotor activity rhythm were significantly lesser in post-DL-induced mice. A reduction in the span of the M1 and M2 motor cortex regions in DL mice and anatomical changes in the dentate gyrus were also seen. Thus, the effects...

Present study examines biological efiects of 2.45GHz microwave radiation in Parkes strain mice. Forty-day-old mice were exposed to CW (continuous wave) microwave radiation (2h/day for 30 days). Locomotor activity was recorded on running wheel for 12 days prior to microwave exposure (pre-exposure), 7 days during the flrst week of exposure (short-term exposure) and another 7-day spell during the last week of the 30-day exposure period (long-term exposure). Morris water maze test was performed from 17th to 22nd day of exposure. At the termination of the exposure, blood was processed for hematological parameters, brain for comet assay, epididymis for sperm count and motility and serum for SGOT (serum glutamate oxaloacetate transaminase) and SGPT (serum glutamate

Pigment-dispersing factors (PDFs) are octadeca-peptides widely distributed in insect optic lobes and brain. In this study, we have purified PDF and determined its amino acid sequence in the cricket Gryllus bimaculatus. Its primary structure was NSEIINSLLGLPKVLNDA-NH(2), homologous to other PDH family members so far reported. When injected into the optic lobe of experimentally blinded adult male crickets, Gryllus-PDF induced phase shifts in their activity rhythms in a phase dependent and dose dependent manner. The resulted phase response curve (PRC) showed delays during the late subjective night to early subjective day and advances during the mid subjective day to mid subjective night. The PRC was different in shape from those for light, serotonin and temperature. These results suggest that PDF plays a role in phase regulation of the circadian clock through a separate pathway from those of other known phase regulating agents.

Biological clocks help organism to adapt temporally to a variety of rhythmic environmental cues. Acute changes in the rhythmicity of entraining cues causes short- to long-term physiological distress in individuals, for example, those occurring during jet-lag after long-haul transmeridial flights, or shift work. Variations in the rate of re-entrainment to a 9 h advanced schedule (simulation of acute Jet-lag/shift work) in the Indian pygmy field mouse, Mus terricolor are reported. Wheel- and lab-acclimated adult male mice were entrained to a 12:12 h light:dark (LD) cycles, followed by a 9 h advance in the LD cycle. In response, these mice either advanced or delayed their activity onsets, with individual variation in the rate and direction. Rapid orthodromic (advancing) re-entrainers exhibited a coincidence of activity onsets with the new dark onset in= 3 days, while gradually advancing re-entrainers took -9 days or more. Delayers (antidromic) also either re-entrained very rapidly (= 2 days), or gradually (-9 days). Acrophase measurement confirmed the direction of the transients, which did not depend on the free-running period. Such different patterns might determine the differential survival of individuals under the pressure of re-entrainment schedules seen in jet-lag and shift work.

Melatonin is known to shift the phase of the locomotor activity rhythm in the field mouse Mus booduga in accordance with a type-I phase response curve (PRC), with phase delays during the subjective day and phase advances during late subjective night and the early subjective day. At CT4 (circadian time 4; i.e. 16 hr. after activity onset) and CT22 of the circadian cycle, a single dose of melatonin (1 mg/kg) is known to evoke maximum delay and maximum advance phase-shifts, respectively. We investigated the dose-dependent responses of the circadian pacemaker of these mice to a single dose of melatonin at the times for maximum delay and maximum advance. The circadian pacemaker responsible for the locomotor activity rhythm in these mice responded to various doses of melatonin in a dose-dependent manner with the magnitude of phase shifts increasing with dose.

The phase shifting effects of the pineal hormone melatonin on the circadian locomotor activity rhythm of the field mouse. Mus booduga was examined at various phases of the circadian cycle using single melatonin injections of two concentrations (10 mg/kg, high dose; and 1 mg/kg, low dose) and two phase response curves (PRCs) were constructed. A single dose of melatonin administered during the early subjective day evoked maximum phase delays, and during the late subjective night evoked phase advances in the locomotor activity rhythm. Other phases of the circadian cycle also responded to melatonin. The interval between circadian time 19 (CT19) and CT2 of the high dose melatonin PRC is marked by significant phase advances, whereas the interval between CT2 and 19 is marked by significant phase delays. A single dose of melatonin of strength 10 mg/kg was found to evoke phase shifts that were of comparable magnitude to those of the phase shifts evoked by natural daylight pulses. Control animals, treated with 50% dimethyl sulfoxide (DMSO), did not respond with phase shifts significantly greater than zero. Significant differences between the shapes of the two melatonin PRCs exist. Further melatonin PRCs appear to have a different time course and wave form relative to light-induced PRC.

The light-induced phase-resetting response of the locomotor activity rhythm in the field mouse Mus booduga was studied at two phases of the circadian cycle known to respond to light stimuli of 15 min duration and 1000 lux intensity with maximum advance (at circadian time 20 [CT20]) and maximum delay phase-shifts (at CT15). The phase-shifts evoked by natural daylight stimuli of various illuminations ranging between 0.001 lux and 10,000 lux and lasting 15 min were estimated. The results clearly demonstrate that the relationship between the phase-shifts and the intensities of light stimuli is nonlinear. Furthermore, a single light stimulus of 0.001 lux, or 0.1 lux intensity for a duration of 15 min, administered at CT20, evoked unequivocal responses; phase delays were observed instead of phase advances. The critical intensities needed for light stimuli of 15 min duration to induce saturating response were calculated and were found to be about 100 lux for CT20 and about 500 lux for CT15. These results suggest that a greater intensity of light is required at the phase CT15 to induce a saturating phase shift than is required at a later phase of the circadian cycle (CT20).

The circadian rhythm of locomotor activity in the nocturnal field mouse Mus booduga has been monitored after an exposure to ultraviolet-A (UV-A; wavelength between 350 and 400 nm) radiation at various hours of the subject's cycle. The magnitude of the phase shift is used to determine the sensitivity of the circadian pacemaker underlying locomotor activity rhythm. It is observed that UV-A shifts the phase of the locomotor activity rhythm in a phase-dependent manner. A phase response curve (PRC) is constructed to depict the time course and waveform of the basic oscillator's sensitivity to UV-A radiation. The UV-A PRC qualitatively resembles the PRC constructed using diffused daylight as stimulus. Furthermore, the phase response characteristics of the circadian pacemaker for UV-A suggest a periodically varying sensitivity to UV-A similar to that to daylight.

The entrainment behaviour of the circadian rhythm of locomotor activity in the field mouse Mus booduga was studied in order to evaluate the role of the animals' free-running period (τ) and the duration of skeleton photoperiods in determining entrainment of animals with τ values beyond and close to the “limits of entrainment”. We predicted that animals with τ lesser than the lower “limit of entrainment” would entrain only to short skeleton photoperiods (≤ 6 h) and not to longer skeleton photoperiods. Experimental animals (n = 25) were entrained to light/dark (LD) 12:12 h schedule, and then subjected to various skeleton photoperiods in which the duration of one of the two intervals of darkness was successively reduced while holding the zeitgeber period (T) constant. Some animals (n = 9) entrained to long as well as short photoperiods, whereas others (n = 5) entrained only to extremely short skeleton photoperiods of 6 h or less. The mean τ of the animals entraining to all photoperiods (23.78 ± 0.22 h) was si...

The entrainment of the circadian rhythm of locomotor activity was studied in the field mouse Mus booduga in order to examine the relationship between the free-running period (tau) and minimum tolerable light pulse interval of the skeleton photoperiods. The animals were entrained under three different light/dark (LD) schedules, each out of phase with the other. They were then subjected to various skeleton photoperiods created by two repeated light pulses (LPs) interrupting darkness. Animals that selected the shorter interval between the LPs as their "subjective night" had significantly shorter tau (23.13 +/- 0.38 h) as compared to those that selected the longer dark interval as subjective night (tau = 23.87 +/- 0.18 h). When the longer dark interval was 12 h, animals selecting that interval as their subjective night included both long-tau and short-tau individuals. When both intervals of darkness were of equal duration, no difference in the selection of subjective night was seen between short and long-tau animals. When the "dusk" LP for the animals that selected the longer dark interval as subjective night was advanced by 2 h to create a new skeleton photoperiod, the number of transient cycles appearing before steady-state entrainment was found to depend on the duration of the photoperiods. When the night defined by the two LPs was reduced below 6h, a dramatic "phase jump" in the activity rhythm was observed, and the initial phase relationship was restored after a relaxation in the night duration. We observed considerable interindividual variation in the "minimum tolerable light pulse interval of skeleton photoperiods," which we suggest may be due to the observed variation in tau among individuals.

Photic phase response curves (PRCs) have been extensively studied in many laboratory-bred diurnal and nocturnal rodents. However, comparatively fewer studies have addressed the effects of photic cues on wild diurnal mammals. Hence, we studied the effects of short durations of light pulses on the circadian systems of the diurnal Indian Palm squirrel, Funambulus pennanti. Adult males entrained to a light-dark cycle (12 h-12 h) were transferred to constant darkness (DD). Free-running animals were exposed to brief light pulses (250 lux) of 15 min, 3 circadian hours (CT) apart (CT 0, 3, 6, 9, 12, 15, 18 and 21). Phase shifts evoked at different phases were plotted against CT and a PRC was constructed. F. pennanti exhibited phase-dependent phase shifts at all the CTs studied, and the PRC obtained was of type 1 at the intensity of light used. Phase advances were evoked during the early subjective day and late subjective night, while phase delays occurred during the late subjective day and early subjective night, with maximum phase delay at CT 15 (-2.04 ± 0.23 h), and maximum phase advance at CT 21 (1.88 ± 0.31 h). No dead zone was seen at this resolution. The free-running period of the rhythm was concurrently lengthened (deceleration) during the late subjective day and early subjective night, while period shortening (acceleration) occurred during the late subjective night. The maximum deceleration was noticed at CT 15 (-0.40 ± 0.09 h) and the maximum acceleration at CT 21 (0.39 ± 0.07 h). A significant positive correlation exists between the phase shifts and the period changes (r = 0.684, p = 0.001). The shapes of both the PRC and period response curve (τRC) qualitatively resemble each other. This suggests that the palm squirrel's circadian system is entrained both by phase and period responses to light. Thus, F. pennanti exhibits robust clock-resetting in response to light pulses.

The objective of this study was to assess whether melatonin accelerates the re- entrainment of locomotor activity after 6 h of advance and delay phase shifts following exposure to LD 12:12 cycle (simulating jet-lag/shift work). An experimental group of adult male field mice Mus booduga were subjected to melatonin (1 mg/kg) through i.p. and the control group were treated with 50 % DMSO. The injections were administered on three consecutive days following 6h of phase advance and delay, at the expected time of "lights off'. The results show that melatonin accelerates the re-entrainment after phase advance (29%) when compared with control mice. In the 6 h phase delay study, the experimental mice (melatonin administered) take more cycles for re-entrainment (51%) than the control. Further, the results suggest that though melatonin may be useful for the treatment of jet-lag caused by eastward flight (phase advance) it may not be useful for westward flight (phase delay) jet-lag.

We report that l-5-hydroxytryptophan (5-HTP), a serotonin precursor, resets the overt circadian rhythm in the Indian pygmy field mouse, Mus terricolor, in a phase- and dose-dependent manner. We used wheel running to assess phase shifts in the free-running locomotor activity rhythm. Following entrainment to a 12:12 h light–dark cycle, 5-HTP (100 mg/kg in saline) was intraperitoneally administered in complete darkness at circadian time (CT)s 0, 3, 6, 9, 12, 15, 18, and 21, and the ensuing phase shifts in the locomotor activity rhythm were calculated. The results show that 5-HTP differentially shifts the phase of the rhythm, causing phase advances from CT 0 to CT 12 and phase delays from CT 12 to CT 21. Maximum advance phase shift was at CT 6 (1.18 ± 0.37 h) and maximum delay was at CT 18 (−2.36 ± 0.56 h). No extended dead zone is apparent. Vehicle (saline) at any CT did not evoke a significant phase shift. Investigations with different doses (10, 50, 100, and 200 mg/kg) of 5-HTP revealed that the phase resetting effect is dose-dependent. The shape of the phase–response curve (PRC) has a strong similarity to PRCs obtained using some serotonergic agents. There was no significant increase in wheel-running activity after 5-HTP injection, ruling out behavioral arousal-dependent shifts. This suggests that this phase resetting does not completely depend on feedback of the overt rhythmic behavior on the circadian clock. A mechanistic explanation of these shifts is currently lacking.

The effect of melatonin on the rate of reentrainment after a 6 h phase delay and a 6 h phase advance in the light-dark (LD) cycle was assayed in the nocturnal field mouse Mus booduga. After a phase delay of 6 h 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 6 h 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 onset and duration of parturition were studied in Megaderma lyra for two successive periods during the years 1989 and 1990. The period of parturition fell between January and May in 1989, and between March and May in 1990. This change in the length of parturition period was not due to variations in the pattern of rainfall when prey items are abundant. The young M. lyra clung continuously for 5–7 days from birth to their mothers whose foraging modality seemed unaffected. Grown-up infants were left at a temple roost while the mother bats foraged. On a few occasions, mothers and infants were also seen at different `night roosts' found close to the temple roost. In all stages of nursing, the lactating mothers had two distinct bouts of foraging, one immediately following emergence (at dusk) and the other during their return (at predawn hours) to their main roost. The mean lactation period in M. lyra was approximately 70 days.

Priyoneel Basu, Muniyandi SingaravelChronobiology Laboratory, Department of Zoology, Banaras Hindu University, Varanasi, IndiaRecently, an editorial in Nature Neuroscience pointed out the need for exercising caution in the use of over-the-counter drinks purporting to promote relaxation and containing, among other substances with chronobiotic activity, L-5-Hydroxytryptophan (5-HTP).1 This reality-check certainly raises an issue worth the attention of scientists who deal with, and laymen who dabble in, biological rhythms. Proprietary and patented formulations often project an image of safety, which is augmented by their over-the-counter availability as attractively packaged nutritional supplements. The allure of these bottled shots of bliss may seem undeniable to the general public. An online search of the words "5-HTP relaxation drink" returns > 7 million websites. Websites promoting these drinks do carry limited warnings or disclaimers (in fine print). The actual concentration of constituents is sometimes not provided in the online information leaflets. Certain websites provide a Natural Standard Editorial Board blinded review,2,3 which summarizes known scientific literature (exhaustively) and mentions likely safe doses. In view of the rising popularity and wide availability of 5-HTP containing drinks, we feel that scientists and the general public alike would profit from an additional nugget of information regarding a previously unforeseen effect of 5-HTP consumption at an inappropriate time, as brought to light by recent literature in the area.View orignal paper by Narsimhan