Use of PVC Conduits by Rats of Various Strains and Ages Housed Singly and in Pairs

This study observed the frequency with which laboratory rats (Rattus norvegicus) entered polyvinylchloride (PVC) conduits placed in their cages to provide environmental enrichment. The study found that use of PVC conduits by Norway rats varied with subjects' strain, age, sex, and housing condition. Adult male Long-Evans rats rarely entered PVC conduits unless housed in pairs, in which case the lighter (presumably subordinate) pair member frequently used the conduit, possibly to avoid contact with his dominant partner. Adult male Sprague-Dawley rats entered PVC conduits only during the illuminated portion of the day-night cycle and only if housed on shelves exposed to direct overhead illumination. Both juvenile rats and female rats made extensive use of PVC conduits throughout the day-night cycle. This article discusses implications of these findings for determining how best to enrich environments in which laboratory rodents are maintained.     

The physiological and behavioral impact of sensory contact among unfamiliar adult mice in the laboratory

Housing mice in the laboratory in groups enables social interaction and is the way a laboratory should house mice. However, adult males show reciprocal aggression and are therefore frequently housed individually. Alternatively, a grid divider, which allows sensory contact by sight and smell but prevents fighting and injuries, can separate mice within 1 cage. This study examined the influence of this housing method on various physiological and behavioral parameters. Adult male mice housed for 10 days with sensory contact to an unfamiliar male displayed significant increases in heart rate (HR), body core temperature (BT), and motor activity (ACT). Furthermore, the mice suffered impaired nest-building behavior and significantly reduced body weight. Conversely, males housed in a similar manner with a female companion showed only a transient elevation of ACT, BT, and HR. Although no clear beneficial effect of housing males with sensory contact to females was evident, this study could not exclude it. On the other hand, housing of mature males in this way leads to sustained detrimental alterations of physiology and behavior, thus implying severe impairment of animal well-being.     

Cooperative social coordination and aggression in male laboratory rats: effects of housing and testosterone

A cooperative behavior, coordinated shuttling by pairs of laboratory rats in a rectangular chamber, can be influenced strongly by an interaction between housing and sex. Males and females learn readily when housed together socially, but individual housing ("isolation") causes severe deficits selectively in males. The aim of the present study was to examine the role of testosterone in the differential effects of housing on cooperation learning. Males of a Sprague-Dawley derived strain were housed socially or individually and treated daily in one of three ways (six groups, n = 6 per group): (1) castrated, injected with oil vehicle (without testosterone); (2) castrated, injected with 500 micrograms testosterone propionate (exogenous TP); and (3) sham operated, injected with oil (intact, endogenous testosterone). Socially housed pairs learned readily in all treatment groups, using strategies of coordination in which stereotyped contact or aggressive interactions were interpolated. Individual housing was associated with a deficit, but only in the TP-treated and intact groups in which some pairs either did not learn or performed poorly. The deficit was associated with violent fighting and extreme and stable differentiation into dominants and subordinates, the latter exhibiting prolonged freezing. Oil-treated castrates, when housed individually, were unimpaired and actually surpassed their socially housed counterparts on some measures. Their success was associated with an increase only in low-level aggression. The housing-hormone interaction in male rats suggests that testosterone influences the capacity to develop cooperative behavior by modulating both aggression and its consequences for the relationship between partners. The use of social interaction models, including cooperation, for the study of behavior-hormone interactions was also discussed.     

Accurate measurement of body weight and food intake in environmentally enriched male Wistar rats

Laboratory animals are crucial in the study of energy homeostasis. In particular, rats are used to study alterations in food intake and body weight. To accurately record food intake or energy expenditure it is necessary to house rats individually, which can be stressful for social animals. Environmental enrichment may reduce stress and improve welfare in laboratory rodents. However, the effect of environmental enrichment on food intake and thus experimental outcome is unknown. We aimed to determine the effect of environmental enrichment on food intake, body weight, behavior and fecal and plasma stress hormones in male Wistar rats. Singly housed 5–7‐week‐old male rats were given either no environmental enrichment, chew sticks, a plastic tube of 67 mm internal diameter, or both chew sticks and a tube. No differences in body weight or food intake were seen over a 7‐day period. Importantly, the refeeding response following a 24‐h fast was unaffected by environmental enrichment. Rearing, a behavior often associated with stress, was significantly reduced in all enriched groups compared to controls. There was a significant increase in fecal immunoglobulin A (IgA) in animals housed with both forms of enrichment compared to controls at the termination of the study, suggesting enrichment reduces hypothalamo‐pituitary‐adrenal (HPA) axis activity in singly housed rats. In summary, environmental enrichment does not influence body weight and food intake in singly housed male Wistar rats and may therefore be used to refine the living conditions of animals used in the study of energy homeostasis without compromising experimental outcome.     

Hormonal responses to female conspecifics in hyperprolactinemic male rats and mice

Exposure to a female results in an acute release of LH and testosterone (T) in normal male rats and mice. This study was conducted to determine whether these hormonal responses are altered in hyperprolactinemic (hyperPRL) male rats in which copulatory behavior is known to be suppressed and in hyperPRL male mice in which it is not. Adult male CDF (F-344) rats were made hyperPRL either by grafting of three anterior pituitaries under the kidney capsule or by treatment with diethylstilbestrol (DES). Exposure of control males to receptive females for 10-15 min produced the expected two- to fourfold statistically significant elevations in plasma LH levels. In contrast, plasma LH levels in pituitary grafted or DES-treated males were not altered by female exposure. Male mice were pituitary grafted (two pituitaries per recipient) or sham-operated and housed individually with a female for 1 week. The resident females were then replaced with novel females in half of the cages and blood samples were taken from the males after 5 min exposure for determination of LH levels or after 45-60 min exposure for T levels. Female-induced LH and T elevations occurred in both hyperPRL and control groups. Failure of hyperPRL male rats to experience an increase in plasma LH levels in response to a female suggests abnormality of mechanisms controlling LHRH release. Suppression of LHRH release may be involved also in the induction of deficits of sexual behavior in these animals.     

The effect of thermopreference on circadian thermoregulation in sprague-dawley and fisher 344 rats

Interstrain differences in thermoregulation of rats are important in biomedical research because subtleties in thermoregulatory sensitivities may greatly affect data collected. Little is known regarding how individual rodent strains differentially utilize behavioral thermal preference to regulate core temperature (Tc). Sprague-Dawley (SD) and Fischer 344 (F344) rats are known to have differences in thermoregulation including heat tolerance and are useful models to study interstrain differences in thermoregulation. Adult male SD and F344 rats of similar body size were implanted with radiotelemetry thermoprobes (DSI) to measure Tc and MA and housed in either a longitudinal temperature gradient with an ambient temperature (Ta) range of ∼15–40 °C to measure selected Ta (STa) or control environment maintained at a Ta of 23 °C. When continuously monitored for 48 h, Tc and MA increased at night, while STa decreased, according to their normal circadian cycle in both strains. SD rats were more active than F344 rats throughout the circadian cycle (SD gradient: day=12.9±1.2 m/h, night=32.1±2.4 m/h; F344 gradient: day=4.1±0.6 m/h, night=16.8±1.8 m/h; p<0.05 interstrain and circadian effects). The STa of each strain was greater during the daytime (SD: 26.4±0.2 °C; F344: 27.8±0.3 °C) than at night (SD: 24.7±0.3 °C; F344: 25.7±0.3 °C) confirming past studies that thermopreference during the day and night is greater than standard room temperature (∼23 °C). Correlations between MA and Tc suggest that MA has a greater effect on Tc in the F344 but not the SD strain when housed in a temperature gradient. There were significant strain differences in Tc depending on whether rats were housed in a temperature gradient. That is, the control F344 rats had a lower Tc during the transition from dark to light compared to rats housed in a gradient. Tc of the SD strain was unaffected by housing in the gradient. Rats are typically housed at a standard room temperature of 23 °C. However, the results demonstrate that when given the opportunity to behaviorally thermoregulate in a temperature gradient, the F344 strain selects a warmer environment that affects the regulation of Tc. This may be important in the experimenters' choice of ambient temperatures to house and study rats and other rodents.     

Housing condition alters immunological and reproductive responses to day length in Siberian hamsters (Phodopus sungorus)

During winter, increased thermoregulatory demands coincide with limited food availability necessitating physiological tradeoffs among expensive physiological processes resulting in seasonal breeding among small mammals. In the laboratory, short winter-like day lengths induce regression of the reproductive tract, but also enhance many aspects of immune function. It remains unspecified the extent to which bolstered immune responses in short days represent enhanced immune function per se compared to long days or represents energetic disinhibition mediated by the regression of the reproductive tract. Cohabitation of male Siberian hamsters with intact female conspecifics can block short-day reproductive regression. We sought to determine whether female cohabitation could also block the enhanced immune function associated with short days. Adult male Siberian hamsters were housed in long or short day lengths in one of three housing conditions: (1) single-housed, (2) housed with a same sex littermate, or (3) housed with an ovariectomized female. Delayed-type hypersensitivity (DTH) responses were assessed after 8 weeks of photoperiod treatment. Housing with an ovariectomized female was not sufficient to block short-day reproductive regression, but prevented short-day enhancement of DTH responses. Housing with a male littermate did not alter reproductive or immune responses in either photoperiod. These data suggest that short day enhancement of immune function is independent of photoperiod-mediated changes in the reproductive system.     

Splanchnic sequestration of amino acids in aged rats: in vivo and ex vivo experiments using a model of isolated perfused liver

Splanchnic sequestration of amino acids (SSAA) is a process observed during aging that leads to decreased peripheral amino acid (AA) availability. The mechanisms underlying SSAA remain unknown. The aim of the present study was to determine whether a high-protein diet could increase nitrogen retention in aged rats by saturating SSAA and whether SSAA could be explained by dysregulation of hepatic nitrogen metabolism. Adult and aged male Sprague-Dawley rats were housed in individual metabolic cages and fed a normal-protein (17% protein) or high-protein diet (27%) for 2 wk. Nitrogen balance (NB) was calculated daily. On day 14, livers were isolated and perfused for 90 min to study AA and urea fluxes. NB was lower in aged rats fed a normal-protein diet than in adults, but a high-protein diet restored NB to adult levels. Isolated perfused livers from aged rats showed decreased urea production and arginine uptake, together with a release of alanine (vs. uptake in adult rats) and a hepatic accumulation of alanine. The in vivo data suggest that SSAA is a saturable process that responds to an increase in dietary protein content. The hepatic metabolism of AA in aged rats is greatly modified, and urea production decreases. This result refutes the hypothesis that SSAA is associated with an increase in AA disposal via urea production.     

Diurnal and circadian rhythm in compound eye of cricket (Gryllus bimaculatus): changes in structure and photon capture efficiency

Day-night changes in rhabdom size of compound eyes were investigated in three groups of crickets (Gryllus bimaculatus): nymphs and adult males and females. In both adults and nymphs, the rhabdoms were larger at night than during a day. In adults, the mean rhabdom occupation ratios (RORs) of ommatidial retinulae at midnight were about two times greater than the values at midday. This change contributes to control of the photon capture efficiency (PCE) of the eye according to photic environment. The RORs of adult males at midnight were higher than those of both adult females and nymphs. This suggests that the PCE of the compound eye of adult males is the greatest of all groups. Under constant darkness, day-night changes in ROR were detected only in adult males, but neither in adult females nor in nymphs. On the other hand, no day-night changes were detected in any experimental group under constant light. These results suggest that the change in rhabdom size between day and night is an adaptation to the photic environment that is controlled mainly by the light-dark (day-night) cycle. However, the change in male adults is induced by an endogenous circadian clock.     

Soy of dietary source plays a preventive role against the pathogenesis of prostatitis in rats.

This study examined the effects of diet on the development of prostatitis in male rats. Adult male rats were placed on either of two specially formulated diets which differed from one another by the presence or absence of soy as the protein source. A third group of rats (control) was fed standard laboratory rat chow which also includes soy as a source of protein. After 11 weeks, it was found that rats maintained on soy-free diet developed prostatitis mainly in the lateral lobe of the prostate. Increased severity and incidence of prostatitis in rats maintained on the soy-free diet coincided with a significant decrease in urinary excretion of various phytoestrogens. There was no evidence of prostatitis in rats maintained on soy-containing diets. Urinary excretion of phytoestrogens in rats maintained on soy-containing diet was also not different from controls. These results suggest that soy as a dietary source plays a protective role against the development of prostatitis in rats, and indicate that the ventral, lateral and dorsal lobes of the rat prostate have different sensitivities to alterations in dietary factors.     

PDE5 Inhibition Improves Object Memory in Standard Housed Rats but Not in Rats Housed in an Enriched Environment: Implications for Memory Models?

Drug effects are usually evaluated in animals housed under maximally standardized conditions. However, it is assumed that an enriched environment (EE) more closely resembles human conditions as compared to maximally standardized laboratory conditions. In the present study, we examined the acute cognition enhancing effects of vardenafil, a PDE5 inhibitor, which stimulates protein kinase G/CREB signaling in cells, in three different groups of male Wistar rats tested in an object recognition task (ORT). Rats were either housed solitarily (SOL) or socially (SOC) under standard conditions, or socially in an EE. Although EE animals remembered object information longer in the vehicle condition, vardenafil only improved object memory in SOL and SOC animals. While EE animals had a heavier dorsal hippocampus, we found no differences between experimental groups in total cell numbers in the dentate gyrus, CA2–3 or CA1. Neither were there any differences in markers for pre- and postsynaptic density. No changes in PDE5 mRNA- and protein expression levels were observed. Basal pCREB levels were increased in EE rats only, whereas β-catenin was not affected, suggesting specific activation of the MAP kinase signaling pathway and not the AKT pathway. A possible explanation for the inefficacy of vardenafil could be that CREB signaling is already optimally stimulated in the hippocampus of EE rats. Since previous data has shown that acute PDE5 inhibition does not improve memory performance in humans, the use of EE animals could be considered as a more valid model for testing cognition enhancing drugs.     

Non-specific neural stimuli and metabolic rhythms in rats.

Ten rats housed in individual metabolism cages in a room next to a teaching laboratory showed rhythmic fluctuations in urination and defaecation. Sectral analysis of the data indicates a weekly rhythm which is attributed to the lack of neural stimuli at the weekend. Regression analysis using a weekly cycle illustrates this effect.     

Diet-induced hyperphagia in the rat is influenced by sex and exercise

Caloric intake is increased in rats fed a diet containing greater fat or sugar than that found in laboratory chow. Because such diet-induced hyperphagia has been studied primarily in sedentary male rats, our goal here was to investigate the effects of sex and exercise on caloric intake of a diet (chow supplemented with sweet milk) chosen for its ability to stimulate hyperphagia. Rats were housed individually in cages that provided access to running wheels, and daily caloric intake of chow alone and then chow plus sweet milk was monitored during sedentary and active conditions. In sedentary rats, chow intake was greater in males compared with females. Wheel running produced similar decreases in chow intake in both sexes. Availability of the chow plus milk diet increased caloric intake compared with that observed in chow-fed rats. This diet-induced hyperphagia was significantly greater in sedentary females (35.7 +/- 3.1% increase) relative to sedentary males (9.1 +/- 2.2% increase). In addition, 35% of sedentary females consuming the chow plus milk diet developed estrous cycle disruptions. Wheel running decreased intake of the chow plus milk diet in both sexes. In active males, diet-induced hyperphagia was abolished; caloric intake was reduced to that observed during chow feeding. In active female rats, diet-induced hyperphagia was attenuated but not abolished; caloric intake of the chow plus milk diet remained greater than that observed during chow feeding. We conclude that female rats are more vulnerable than male rats to this form of diet-induced hyperphagia.     

Common variations in the pretest environment influence genotypic comparisons in models of anxiety

The behavioral characterization of rodent strains in different studies and laboratories can provide unreplicable results even when genotypes are kept constant and environmental control is maximized. In the present study, the influence of common laboratory environmental variables and their interaction with genotype on the results of behavioral tests of anxiety/emotionality were investigated. To this end, the inbred rat strains Lewis (LEW) and spontaneously hypertensive rats (SHR), which are known to differ for numerous emotionality-related behaviors, were tested in the open field (OF), elevated plus maze (EPM) and black/white box (BWB), while three environmental factors were systematically controlled and analyzed: (1) the experimenter handling the animal (familiar or unfamiliar); (2) the position of the home cage (top or bottom shelf of the rack) and (3) the behavioral state of the animal immediately before the test (arousal or rest). Experimenter familiarity did not alter the behavior of rats in the OF. Cage position, on the other hand, influenced the behavior in the OF and BWB, with rats housed in top cages appearing less anxious than those housed in the bottom. In the BWB (but not in the OF), these effects were genotype dependent. Finally, the behavioral state of the animals prior to testing altered the results of the EPM in a strain-dependent manner, with some anxiety-related genotypic differences being found only among rats that were aroused in their home cages. This study showed that common variations in the laboratory environment interact with genotype in behavioral tests of anxiety/emotionality. Recognizing and understanding such variations can help in the design of more effective experiments.     

Phenotypic differences in the GnRH neuronal system of deer mice Peromyscus maniculatus under a natural short photoperiod

The neural mechanisms by which short photoperiod induces gonadal regression among seasonally breeding mammals are not well understood. One hypothesis suggests that the proximate cause of seasonal gonadal regression is a photoperiod-induced modification in GnRH secretion. This hypothesis is indirectly supported by our recent findings using immunocytochemistry which identified specific photoperiod-induced adjustments in the number and morphology of GnRH containing neurones between reproductively competent and reproductively regressed laboratory housed male deer mice. Herein, we report that the GnRH neuronal system is similarly affected in reproductively responsive and nonresponsive wild male deer mice Peromyscus maniculatus exposed to a natural short photoperiod. The distribution of immunoreactive (IR)-GnRH neurones was nearly identical in field caught animals and those housed under artificial photoperiod in the laboratory. Compared with reproductively nonresponsive males, reproductively responsive mice from the field population possessed a greater total number of IR-GnRH neurones, a greater number of IR-GnRH neurones within the lateral hypothalamus, and a greater proportion of bipolar IR-GnRH neurones. Each of these distributional and morphological characters was consistent with our findings in laboratory housed male deer mice exposed to an artificial short photoperiod. Taken together, these data underscore the validity of using an artificial photoperiod to evaluate seasonal adjustments in reproductive function in the laboratory.     

S20098 AFFECTS THE FREE-RUNNING RHYTHMS OF BODY TEMPERATURE AND ACTIVITY AND DECREASES LIGHT-INDUCED PHASE DELAYS OF CIRCADIAN RHYTHMS OF THE RAT

Mammalian endogenous circadian rhythms are entrained to the environmental day-night cycle by light exposure. Melatonin is involved in this entrainment by signaling the day-night information to the endogenous circadian pacemaker. Furthermore, melatonin is known to affect the circadian rhythm of body temperature directly. A striking property of the endogenous melatonin signal is its synthesis pattern, characterized by long-term elevated melatonin levels throughout the night. In the present study, the influence of prolonged treatment with the melatonin agonist S20098 during the activity phase of free-running rats was examined. This was achieved by giving S20098 in the food. The free-running body temperature and activity rhythms were studied. The present study shows that enhancement of the melatonin signal, using S20098, affected the free-running rhythm by gradual phase advances of the start of the activity phase, consequently causing an increase in length of the activity phase. A well-known feature of circadian rhythms is its time-dependent sensitivity for light. Light pulse exposure of an animal housed under continuous dark conditions can cause a phase shift of the circadian pacemaker. Therefore, in a second experiment, the influence of melatonin receptor stimulation on the sensitivity of the pacemaker to light was examined by giving the melatonin agonist S20098 in the food during 1 day prior to exposure to a 60-min light pulse of 0, 1.5, 15, or 150 lux given at circadian time (CT) 14. S20098 pretreatment caused a diminished lightpulse- induced phase shift when a light pulse of low light intensity (1.5 lux) was given. S20098 treatment via the food was sufficient to exert chronobiotic activity, and S20098 treatment resulting in prolonged overstimulation of melatonin receptors is able to attenuate the effect of light on the circadian timing system. (Chronobiology International, 18(5), 781-799, 2001)     

Calcium rather than calcitonin is dominant to mediate gastric emptying in thyroidectomized rats

Both calcium and calcitonin are important in mediating gastrointestinal motility. Present study tried to study what was the dominant role of calcitonin or calcium replacement on the gastric emptying in thyroidectomized animals. Adult Sprague-Dawley male rats received thyroidectomy or sham operation and then housed for two weeks until motility study, which was conducted using radiochromium to measure gastric emptying. Before motility study these rats were i.p. injected with saline or human calcitonin in the doses of 0.1, 1 and 10 microgM/kg, respectively. Another group of thyroidectomized rats received i.v. infusion of saline or CaCl2 for 30 min before motility study. Among thyroidectomized rats, neither saline nor various doses of calcitonin treatment disturbed gastric emptying compared to this of sham operated rats. Thyroidectomy diminished plasma calcium level, however, additional calcitonin treatment did not restore the suppressed calcium level (P<0.01). Of rats following saline or CaCl2 infusion, thyroidectomy did not change gastric emptying, whereas CaCl2 infusion enhanced gastric emptying (P<0.05). In conclusion, exogenous calcium treatment further enhances gastric emptying in thyroidectomized rats, whereas calcitonin replacement has no effect on gastric emptying. We suggest that calcium rather than calcitonin is dominant to mediate gastric emptying.     

Effect of Moringa oleifera leaves on hematological profile of fluorosis affected rats

Fluorosis is a metabolic disease that is endemic in nearly 25 countries with India being one of the most affected. It primarily affects the bone and the teeth. Moringa oleifera (MO) leaves are known to reduce the effect of fluorosis on various tissues. Therefore, it is of interest to document the effect of Moringa oleifera leaves on the hematological profile of fluorosis affected rats. Twenty four Sprague Dawley rats were housed two per cage in a room with 12 hours light and 12 hours dark cycle. The rats were allowed to adjust to the laboratory environment for about one to two weeks before the beginning of the study. This study reveals that MO leaves is effective in reducing the plasma fluoride content. It also helps in improving the Hb % and RBC count in fluorosis affected rats. Data shows that Moringa olifera leaves powder is effective in reducing the plasma fluoride content. It also helps in improving the Hemoglobin percentage & Red Blood Cell count in fluorosis affected rats.     

Effect of Post-Weaning Individual Housing on Autonomic Responses in Male Rats to Sexually Receptive Female Rats

Post-weaning individual housing induces significant alterations in the reward system of adult male rats presented with sexually receptive female rats. In this study, we examined the effects of post-weaning individual housing on autonomic nervous activity in adult male rats during encounters with sexually receptive female rats to assess whether different affective states depending on post-weaning housing conditions are produced. Changes in heart rate and spectral parameters of heart rate variability indicated that in post-weaning individually housed male rats, both sympathetic and parasympathetic activity increased with no change in the sympathovagal balance, while in post-weaning socially housed male rats, both sympathetic and parasympathetic activity decreased with a predominance of parasympathetic activity. These two patterns of shifts in sympathovagal balances closely resembled changes in autonomic nervous activity with regard to classical appetitive conditioning in male rats. The autonomic changes in male rats housed individually after weaning corresponded to changes associated with the reward-expecting state evoked by the conditioned stimulus, and the autonomic changes observed in male rats housed socially after weaning corresponded to changes associated with the reward-receiving state evoked by the unconditioned stimulus. These results suggest that different affective states were induced in adult male rats during sexual encounters depending on male–male social interactions after weaning. The remarkable change caused by post-weaning individual housing may be ascribed to alteration of the reward system during sexual encounters induced by deficiency of intermale social communication after weaning.     

S20098 AFFECTS THE FREE-RUNNING RHYTHMS OF BODY TEMPERATURE AND ACTIVITY AND DECREASES LIGHT-INDUCED PHASE DELAYS OF CIRCADIAN RHYTHMS OF THE RAT

Mammalian endogenous circadian rhythms are entrained to the environmental day-night cycle by light exposure. Melatonin is involved in this entrainment by signaling the day-night information to the endogenous circadian pacemaker. Furthermore, melatonin is known to affect the circadian rhythm of body temperature directly. A striking property of the endogenous melatonin signal is its synthesis pattern, characterized by long-term elevated melatonin levels throughout the night. In the present study, the influence of prolonged treatment with the melatonin agonist S20098 during the activity phase of free-running rats was examined. This was achieved by giving S20098 in the food. The free-running body temperature and activity rhythms were studied. The present study shows that enhancement of the melatonin signal, using S20098, affected the free-running rhythm by gradual phase advances of the start of the activity phase, consequently causing an increase in length of the activity phase. A well-known feature of circadian rhythms is its time-dependent sensitivity for light. Light pulse exposure of an animal housed under continuous dark conditions can cause a phase shift of the circadian pacemaker. Therefore, in a second experiment, the influence of melatonin receptor stimulation on the sensitivity of the pacemaker to light was examined by giving the melatonin agonist S20098 in the food during 1 day prior to exposure to a 60-min light pulse of 0, 1.5, 15, or 150 lux given at circadian time (CT) 14. S20098 pretreatment caused a diminished lightpulse- induced phase shift when a light pulse of low light intensity (1.5 lux) was given. S20098 treatment via the food was sufficient to exert chronobiotic activity, and S20098 treatment resulting in prolonged overstimulation of melatonin receptors is able to attenuate the effect of light on the circadian timing system. (Chronobiology International, 18(5), 781–799, 2001)