Constant light and single housing alter novelty-induced locomotor activity and sociability in female Swiss Webster mice.

OBJECTIVE: Light exposure at night is known to produce behavioral aberrations in both human and animal models. One way to mimic light-at-night is through constant light exposure (LL), wherein animals are placed in an environment where a dark phase never occurs. Additionally, the type of housing condition for the rodents in experiments - grouped-housed vs singly-housed - can produce different behavioral responses, even in female mice. This study investigated whether LL produces alterations to emotionality and sociability, and whether group housing can alleviate some of those negative behavioral outcomes in female mice. METHODS: Female Swiss Webster mice were placed into group or single housing conditions and either into a standard 12:12 light:dark cycle or LL. Novelty-induced (open-field, light-dark box) and circadian locomotor activity, sociability, and serum oxytocin were measured during the middle of the day. RESULTS: LL and group-housing produced alterations to circadian home-cage activity and increases novelty-induced locomotor activity in the open-field and light-dark box. LL led to increased aggression in both group-housed and single-housed mice, while single-housed/LL mice showed reduced encounters towards the social mouse. Group-housed/LL mice exhibited increased interactions with the empty enclosure. Additionally, both LL and group-housing increased oxytocin levels. CONCLUSIONS: The increase in oxytocin may be a contributing factor to why female mice exhibit increased aggression and other impaired social behaviors in LL. Socialization via group housing was ineffective in reducing the negative sociability seen in mice under LL. These results indicate that aberrant light exposure and circadian misalignment are correlated with impaired social behaviors and emotionality.

Estradiol Regulates Circadian Responses to Acute and Constant Light Exposure in Female Mice.

Sex hormones are well known to modulate circadian timekeeping as well as the behavioral and physiological responses to circadian disruption. Gonadectomy, reducing the amount of circulating gonadal hormones, in males and females produces alterations to the free-running rhythm and the responses to light exposure by the central oscillator of the suprachiasmatic nucleus (SCN). In this study, we tested whether estradiol plays a role in regulating the circadian responses to acute (light pulses) and chronic light exposure (constant light [LL] vs standard light:dark [LD] cycle) in female C57BL6/NJ mice. Mice were either ovariectomized or given sham surgery and given a placebo (P) or estradiol (E) pellet for hormone replacement so that there were 6 groups: (1) LD/Sham, (2) LL/Sham, (3) LD/OVX + P, (4) LL/OVX + P, (5) LD/OVX + E, and (6) LL/OVX + E. After 65 days of light cycle exposure, blood and SCNs were removed and serum estradiol plus SCN estradiol receptor alpha (ERα) and estradiol receptor beta (ERß) were measured via ELISA. The OVX + P mice exhibited shorter circadian periods and were more likely to become arrhythmic in LL compared with mice with intact estradiol (sham or E replacement mice). The OVX + P mice exhibited reduced circadian robustness (power) and reduced circadian locomotor activity in both LD and LL compared with sham controls or OVX + E mice. The OVX + P mice also exhibited later activity onsets in LD and attenuated phase delays, but not advances, when given a 15-min light pulse compared with estradiol intact mice. LL led to reductions in ERß, but not ERα, regardless of the surgery type. These results indicate that estradiol can modulate the effects of light on the circadian timing system and that estradiol can enhance responses to light exposure and provide protection against a loss of circadian robustness.

Strain specific behavioral and physiological responses to constant light in male CBA/J and CBA/CaJ mice.

OBJECTIVE: Being visually impaired increases the likelihood of sleep disorders and altered behavior. This study investigated physiological and behavioral differences in two similar mice substrains when exposed to constant light (LL) - CBA/J with retinal degeneration and CBA/CaJ mice (no retinal degeneration). MATERIAL AND METHODS: Male CBA/J and CBA/CaJ mice were placed into a 12:12 light:dark cycle or constant light (LL). Open field behavior, metabolic markers, and home-cage circadian activity were observed. RESULTS: CBA/CaJ mice have greater circadian period lengthening, increased weight gain, reduced glucose, and increased novelty-induced locomotor activity in LL, compared to CBA/J mice. LL reduced thyroid hormone and insulin in both substrains. DISCUSSION: While several baseline substrain differences were elucidated, CBA/CaJ mice were more effected by the exposure to LL than the blind CBA/J mice. These results illustrate that LL causes alterations in physiology and behavior and that circadian photoreceptivity might contribute to these effects.

The timing of fasting leads to different levels of food consumption and PYY3-36 in nocturnal mice.

PURPOSE: The daily circadian cycle is known to modulate both feeding behavior and metabolism. As such, the timing of food consumption can play a role in regulating overall health. The purpose of this study is to determine whether fasting at different times of the day alters subsequent food consumption and levels of PYY3-36, a hormone secreted after a meal which inhibits appetite. METHODS: Separate groups of mice were fasted at different times of the day: (1) start of the day, (2) middle of the day, (3) start of the night, and (4) middle of the night, and either injected with vehicle or PYY3-36 to assess their subsequent food consumption patterns, PYY3-36 levels, and glucose and insulin levels. We also investigated whether light exposure during the night would alter food consumption and PYY3-36 levels after fasting. RESULTS: Mice fasted during the start of the daytime exhibited increased food consumption post-fast compared to mice fasted during the night. Injections of PYY3-36 during the night were more effective in reducing food consumption compared to PYY3-36 administration during the day. Constant light exposure suppressed food consumption after fasting and increased fasting PYY3-36 levels. CONCLUSIONS: These results indicate that mice exhibit distinct food consumption patterns after being presented with a fast at different times of the day. Light exposure also modulates both food consumption after a fast and levels of PYY3-36.

Substrain specific behavioral responses in male C57BL/6N and C57BL/6J mice to a shortened 21-hour day and high-fat diet.

Altered circadian rhythms have negative consequences on health and behavior. Emerging evidence suggests genetics influences the physiological and behavioral responses to circadian disruption. We investigated the effects of a 21 h day (T = 21 cycle), with high-fat diet consumption, on locomotor activity, explorative behaviors, and health in male C57BL/6J and C57BL/6N mice. Mice were exposed to either a T = 24 or T = 21 cycle and given standard rodent chow (RC) or a 60% high-fat diet (HFD) followed by behavioral assays and physiological measures. We uncovered numerous strain differences within the behavioral and physiological assays, mainly that C57BL/6J mice exhibit reduced susceptibility to the obesogenic effects of (HFD) and anxiety-like behavior as well as increased circadian and novelty-induced locomotor activity compared to C57BL/6N mice. There were also substrain-specific differences in behavioral responses to the T = 21 cycle, including exploratory behaviors and circadian locomotor activity. Under the 21-h day, mice consuming RC displayed entrainment, while mice exposed to HFD exhibited a lengthening of activity rhythms. In the open-field and light-dark box, mice exposed to the T = 21 cycle had increased novelty-induced locomotor activity with no further effects of diet, suggesting daylength may affect mood-related behaviors. These results indicate that different circadian cycles impact metabolic and behavioral responses depending on genetic background, and despite circadian entrainment.

Male C57BL6/N and C57BL6/J Mice Respond Differently to Constant Light and Running-Wheel Access.

Previous studies have shown that exposure to circadian disruption produces negative effects on overall health and behavior. More recent studies illustrate that strain differences in the behavioral and physiological responses to circadian disruption exist, even if the strains have similar genetic backgrounds. As such, we investigated the effects of constant room-level light (LL) with running-wheel access on the behavior and physiology of male C57BL6/J from Jackson Laboratories and C57BL6/N from Charles River Laboratories mice. Mice were exposed to either a 12:12 light-dark (LD) cycle or LL and given either a standard home cage or a cage with a running-wheel. Following 6 weeks of LD or LL, their response to behavioral assays (open-field, light-dark box, novel object) and measures of metabolism were observed. Under standard LD, C57BL6/J mice exhibited increased locomotor activity and reduced exploratory behavior compared to C57BL6/N mice. In LL, C57BL6/J mice had greater period lengthening and increased anxiety, while C57BL6/N mice exhibited increased weight gain and no change in exploratory behavior. C57BL6/J mice also decreased exploration with running-wheel access while C57BL6/N mice did not. These results further demonstrate that C57BL/6 substrains exhibit different behavioral and physiological responses to circadian disruption and wheel-running access.

Constant light alters serum hormone levels related to thyroid function in male CD-1 mice.

Disruptions to the circadian rhythm can lead to altered metabolism. Modification of thyroid function may be a reason why circadian misalignment may contribute to future metabolic disorders. We investigated whether circadian disruption through constant light (LL) can lead to variations in hormone levels associated with thyroid function. Mice were exposed to LL or a 12:12 Light:Dark (LD) cycle for 6 weeks; then glucose tolerance and thyroid hormone levels were measured at ZT 6 and ZT 18. There was day/night variation in glucose tolerance, but LL had no effect. LL reduced TSH, increased fT4, and abolished day/night variation in fT3 and leptin. These findings illustrate that LL alters thyroid-related hormones, providing evidence of a link between circadian disruption and thyroid function.

The behavioral and physiological effects of high-fat diet and alcohol consumption: Sex differences in C57BL6/J mice.

BACKGROUND AND OBJECTIVE: Animal studies can be a great tool to investigate sex differences in a variety of different ways, including behavioral and physiological responses to drug treatments and different "lifestyle variables" such as diets. Consumption of both high-fat diets and alcohol is known to affect anxiety behaviors and overall health. This project investigated how high-fat diet and alcohol access and its combination affected the behavior and physiology of male and female C57BL/6J mice. METHOD: Mice were separated into three food groups: high-fat diet, 10% fat diet, and regular chow, and each group was paired with either water or 10% alcohol. Behavioral assays included diet and alcohol preference, light-dark box, open field, and feeding and drinking measurements. Physiological measures included glucose tolerance tests and measurement of brain-derived neurotrophic factor, insulin, and leptin levels. RESULTS: Females and males differed in the open field, as male mice decreased activity, while females increased activity when consuming high-fat diet. While females consumed more ethanol than males, alcohol consumption was able to improve glucose tolerance and increase anxiety in both sexes. Lastly, females were more resistant to the physiological changes caused by high-fat diet than males, as females consuming high-fat diet exhibited decreased insulin secretion, less change to brain-derived neurotrophic factor levels, and better glucose tolerance than males consuming high-fat diet. CONCLUSION: These results suggest that the response to high-fat diet and alcohol consumption is sex dependent and that males are more affected both behaviorally and physiologically by high-fat diet compared to females.

Removal of a high-fat diet, but not voluntary exercise, reverses obesity and diabetic-like symptoms in male C57BL/6J mice.

OBJECTIVE: Both the consumption of high-fat diets and exercise are known to produce alterations in metabolism and behavior. This study focuses on the effects of a change to a low-fat diet from a high-fat diet and voluntary exercise on obesity, type-2 diabetic-like symptoms, and locomotor behavior in male C57BL/6J mice. DESIGN: Mice were initially given either a high-fat diet or regular chow, along with a cage with a running-wheel to mimic exercise, or one without, to determine to what extend exercise affects these symptoms. Then half of the mice given a high-fat diet were switched to regular chow to ascertain if the switch in diet would improve type-2 diabetic-like and obesity symptoms. RESULTS: Wheel-running alone produced an improvement in insulin in mice continuously fed a high-fat diet (p=0.006), but running-wheels did not produce any further improvements in mice with regular chow replacement (p=0.999) or in controls (p=0.996). Replacement of a high-fat diet with regular chow led to physiological improvements in insulin (p=0.012) and leptin (p <0.001), glucose tolerance (p <0.001), and obesity (p <0.001), more so than exercise alone. Mice consuming a high-fat diet without a wheel exhibited reduced home-cage activity compared to controls after the diet switch (p=0.030), while no reduction was found in running-wheel activity between high-fat diet and regular chow consuming mice after switching diets (p=0.516). CONCLUSIONS: These results suggest that exercise is only partially beneficial to improving health outcomes in mice consuming a high-fat diet, whereas incorporating a better diet, even without exercise, improves quality of health and can suppress T2DM symptoms and related conditions more so than exercise alone.

The Phenotypic Effects of Royal Jelly on Wild-Type D. melanogaster Are Strain-Specific.

The role for royal jelly (RJ) in promoting caste differentiation of honeybee larvae into queens rather than workers is well characterized. A recent study demonstrated that this poorly understood complex nutrition drives strikingly similar phenotypic effects in Drosophila melanogaster, such as increased body size and reduced developmental time, making possible the use of D. melanogaster as a model system for the genetic analysis of the cellular mechanisms underlying RJ and caste differentiation. We demonstrate here that RJ increases the body size of some wild-type strains of D. melanogaster but not others, and report significant delays in developmental time in all flies reared on RJ. These findings suggest that cryptic genetic variation may be a factor in the D. melanogaster response to RJ, and should be considered when attempting to elucidate response mechanisms to environmental changes in non-honeybee species.

Voluntary wheel-running attenuates insulin and weight gain and affects anxiety-like behaviors in C57BL6/J mice exposed to a high-fat diet.

It is widely accepted that lifestyle plays a crucial role on the quality of life in individuals, particularly in western societies where poor diet is correlated to alterations in behavior and the increased possibility of developing type-2 diabetes. While exercising is known to produce improvements to overall health, there is conflicting evidence on how much of an effect exercise has staving off the development of type-2 diabetes or counteracting the effects of diet on anxiety. Thus, this study investigated the effects of voluntary wheel-running access on the progression of diabetes-like symptoms and open field and light-dark box behaviors in C57BL/6J mice fed a high-fat diet. C57BL/6J mice were placed into either running-wheel cages or cages without a running-wheel, given either regular chow or a high-fat diet, and their body mass, food consumption, glucose tolerance, insulin and c-peptide levels were measured. Mice were also exposed to the open field and light-dark box tests for anxiety-like behaviors. Access to a running-wheel partially attenuated the obesity and hyperinsulinemia associated with high-fat diet consumption in these mice, but did not affect glucose tolerance or c-peptide levels. Wheel-running strongly increased anxiety-like and decreased explorative-like behaviors in the open field and light-dark box, while high-fat diet consumption produced smaller increases in anxiety. These results suggest that voluntary wheel-running can assuage some, but not all, of the physiological problems associated with high-fat diet consumption, and can modify anxiety-like behaviors regardless of diet consumed.

Mutations in the circadian gene period alter behavioral and biochemical responses to ethanol in Drosophila.

Clock genes, such as period, which maintain an organism's circadian rhythm, can have profound effects on metabolic activity, including ethanol metabolism. In turn, ethanol exposure has been shown in Drosophila and mammals to cause disruptions of the circadian rhythm. Previous studies from our labs have shown that larval ethanol exposure disrupted the free-running period and period expression of Drosophila. In addition, a recent study has shown that arrhythmic flies show no tolerance to ethanol exposure. As such, Drosophila period mutants, which have either a shorter than wild-type free-running period (perS) or a longer one (perL), may also exhibit altered responses to ethanol due to their intrinsic circadian differences. In this study, we tested the initial sensitivity and tolerance of ethanol exposure on Canton-S, perS, and perL, and then measured their Alcohol Dehydrogenase (ADH) and body ethanol levels. We showed that perL flies had slower sedation rate, longer recovery from ethanol sedation, and generated higher tolerance for sedation upon repeated ethanol exposure compared to Canton-S wild-type flies. Furthermore, perL flies had lower ADH activity and had a slower ethanol clearance compared to wild-type flies. The findings of this study suggest that period mutations influence ethanol induced behavior and ethanol metabolism in Drosophila and that flies with longer circadian periods are more sensitive to ethanol exposure.

Long-term wheel-running and acute 6-h advances alter glucose tolerance and insulin levels in TALLYHO/JngJ mice.

Studies have shown a relationship between circadian rhythm disruptions and type-2 diabetes. This investigation examined the effects of circadian disruption (6-h phase advances) on the progression of diabetes in a type-2 diabetic mouse model -TALLYHO/JngJ - and whether wheel-running can alleviate the effects of the phase advances. 6-h advances alter fasting glucose, glucose tolerance and insulin production. Wheel-running reduced body mass, improved glucose tolerance and reduced insulin in TALLYHO/JngJ and alleviated some of the changes in diabetic symptoms due to 6-h advances. These results indicate that individuals with type-2 diabetes can benefit from physical activity and exercise can be a countermeasure to offset the effects of an acute phase advance.

Alcohol and lithium have opposing effects on the period and phase of the behavioral free-running activity rhythm.

Bipolar patients have a high prevalence of comorbid alcohol use and abuse disorders, while chronic alcohol drinking may increase the presence and severity of certain symptoms of bipolar disorder. As such, there may be many individuals that are prescribed lithium to alleviate the manic symptoms of bipolar disorder, but also drink alcohol concurrently. In addition, both alcoholics and individuals with bipolar disorder often exhibit disruptions to their sleep-wake cycles and other circadian rhythms. Interestingly, both ethanol and lithium are known to alter both the period and the phase of free-running rhythms in mammals. While lithium is known to lengthen the period, ethanol seems to shorten the period and attenuate the responses to acute light pulses. Therefore, the present study aimed to determine whether ethanol and lithium have opposing effects on the circadian pacemaker when administered together. C57BL/6J mice were provided drinking solutions containing lithium, alcohol, or both, and their free-running rhythms along with their response to photic phase shifts were investigated. Mice treated with lithium displayed period lengthening, which was almost completely negated when ethanol was added. Moreover, ethanol significantly attenuated light-induced phase delays while the addition of lithium partially restored this response. These results indicate that alcohol and lithium have opposing effects on behavioral circadian rhythms. Individuals with bipolar disorder who are prescribed lithium and who drink alcohol might be inadvertently altering their sleep and circadian cycles, which may exacerbate their symptoms.

Larval ethanol exposure alters free-running circadian rhythm and per Locus transcription in adult D. melanogaster period mutants.

Alcohol consumption causes disruptions in a variety of daily rhythms, including the circadian free-running rhythm. A previous study conducted in our laboratories has shown that larval ethanol exposure alters the free-running period in adult Canton-S Drosophila melanogaster. Few studies, however, have explored the effect of alcohol exposure on organisms exhibiting circadian periods radically different than (normal) 24-h. We reared Canton-S, period long, and period short Drosophila melanogaster larvae on 10%-ethanol supplemented food, and assessed their adult free-running locomotor activity and period transcript at ZT 12. We demonstrate that in Canton-S larval ethanol exposure shortens the adult free-running locomotor activity but does not significantly alter period mRNA levels at ZT 12. Period long mutants exposed to larval ethanol had significantly shortened adult free-running locomotor activity rhythms and decreased period mRNA levels, while period short mutants lengthened their free-running rhythm and showed increased period mRNA levels at ZT 12 after being exposed to larval ethanol. These results indicate that the effects of ethanol on the circadian clock might depend upon the baseline circadian period of the organism or that period mutant gene expression is sensitive to developmental ethanol treatment.

Larval ethanol exposure alters adult circadian free-running locomotor activity rhythm in Drosophila melanogaster.

Alcohol consumption causes disruptions in a variety of daily rhythms, including the sleep-wake cycle. Few studies have explored the effect of alcohol exposure only during developmental stages preceding maturation of the adult circadian clock, and none have examined the effects of alcohol on clock function in Drosophila. This study investigates developmental and behavioral correlates between larval ethanol exposure and the adult circadian clock in Drosophila melanogaster, a well-established model for studying circadian rhythms and effects of ethanol exposure. We reared Drosophila larvae on 0%, 10%, or 20% ethanol-supplemented food and assessed effects upon eclosion and the free-running period of the circadian rhythm of locomotor activity. We observed a dose-dependent effect of ethanol on period, with higher doses resulting in shorter periods. We also identified the third larval instar stage as a critical time for the developmental effects of 10% ethanol on circadian period. These results demonstrate that developmental ethanol exposure causes sustainable shortening of the adult free-running period in Drosophila melanogaster, even after adult exposure to ethanol is terminated, and suggests that the third instar is a sensitive time for this effect.

Effects of withdrawal from chronic intermittent ethanol vapor on the level and circadian periodicity of running-wheel activity in C57BL/6J and C3H/HeJ mice.

BACKGROUND: Alcohol withdrawal is associated with behavioral and chronobiological disturbances that may persist during protracted abstinence. We previously reported that C57BL/6J (B6) mice show marked but temporary reductions in running-wheel activity, and normal free-running circadian rhythms, following a 4-day chronic intermittent ethanol (CIE) vapor exposure (16 hours of ethanol vapor exposure alternating with 8 hours of withdrawal). In the present experiments, we extend these observations in 2 ways: (i) by examining post-CIE locomotor activity in C3H/HeJ (C3H) mice, an inbred strain characterized by high sensitivity to ethanol withdrawal, and (ii) by directly comparing the responses of B6 and C3H mice to a longer-duration CIE protocol. METHODS: In Experiment 1, C3H mice were exposed to the same 4-day CIE protocol used in our previous study with B6 mice (referred to here as the 1-cycle CIE protocol). In Experiment 2, C3H and B6 mice were exposed to 3 successive 4-day CIE cycles, each separated by 2 days of withdrawal (the 3-cycle CIE protocol). Running-wheel activity was monitored prior to and following CIE, and post-CIE activity was recorded in constant darkness to allow assessment of free-running circadian period and phase. RESULTS: C3H mice displayed pronounced reductions in running-wheel activity that persisted for the duration of the recording period (up to 30 days) following both 1-cycle (Experiment 1) and 3-cycle (Experiment 2) CIE protocols. In contrast, B6 mice showed reductions in locomotor activity that persisted for about 1 week following the 3-cycle CIE protocol, similar to the results of our previous study using a 1-cycle protocol in this strain. Additionally, C3H mice showed significant shortening of free-running period following the 3-cycle, but not the 1-cycle, CIE protocol, while B6 mice showed normal free-running rhythms. CONCLUSIONS: These results reveal genetic differences in the persistence of ethanol withdrawal-induced hypo-locomotion. In addition, chronobiological alterations during extended abstinence may depend on both genetic susceptibility and an extended prior withdrawal history. The present data establish a novel experimental model for long-term behavioral and circadian disruptions associated with ethanol withdrawal.

Circadian wheel-running activity during withdrawal from chronic intermittent ethanol exposure in mice.

Alcohol withdrawal is associated with affective-behavioral disturbances in both human alcoholics and in animal models. In general, these phenomena are potentiated by increased alcohol exposure duration and by prior withdrawal episodes. Previous studies have also reported locomotor hypoactivity during ethanol withdrawal in rats and mice, but only in novel test environments and not in the home cage. In the present study, we examined the effects of withdrawal from chronic intermittent ethanol (CIE) vapor exposure on the level and circadian periodicity of wheel-running activity in C57BL/6J mice. CIE treatment resulted in reductions in wheel-running activity compared with plain-air controls that persisted for about 1 week after withdrawal. Analysis of circadian waveforms indicated that reduced activity occurred throughout the night phase, but that daily-activity patterns were otherwise unaltered. CIE failed to alter free-running circadian period or phase in animals maintained under constant darkness. These results show that ethanol withdrawal can result in locomotor hypoactivity even in the habitual, home-cage environment, and suggest that withdrawal-related reductions in wheel-running activity may reflect the specific motivational significance of this behavior.

Chronic ethanol intake alters circadian phase shifting and free-running period in mice.

Chronic alcohol intake is associated with widespread disruptions in sleep and circadian rhythms in both human alcoholics and in experimental animals. Recent studies have demonstrated that chronic and acute ethanol treatments alter fundamental properties of the circadian pacemaker--including free-running period and responsiveness to photic and nonphotic phase-shifting stimuli--in rats and hamsters. In the present work, the authors extend these observations to the C57BL/6J mouse, an inbred strain characterized by very high levels of voluntary ethanol intake and by reliable and stable free-running circadian activity rhythms. Mice were housed individually in running-wheel cages under conditions of either voluntary or forced ethanol intake, whereas controls were maintained on plain water. Forced ethanol intake significantly attenuated photic phase delays (but not phase advances) and shortened free-running period in constant darkness, but voluntary ethanol intake failed to affect either of these parameters. Thus, high levels of chronic ethanol intake, beyond those normally achieved under voluntary drinking conditions, are required to alter fundamental circadian pacemaker properties in C57BL/6J mice. These observations may be related to the relative ethanol insensitivity displayed by this strain in several other phenotypic domains, including ethanol-induced sedation, ataxia, and withdrawal. Additional experiments will investigate chronobiological sensitivity to ethanol in a range of inbred strains showing diverse ethanol-related phenotypes.

Chronic ethanol intake modulates photic and non-photic circadian phase responses in the Syrian hamster.

Chronic alcohol intake disrupts sleep and other circadian biological rhythms in both human alcoholics and in experimental animals. Recent studies from our laboratory indicate that these effects may be due, in part, to ethanol-induced alterations in fundamental properties of the circadian pacemaker. The present study explored the effects of chronic voluntary ethanol intake (25% v/v) on circadian phase responses to both photic and non-photic stimuli in Syrian hamsters. Hamsters were used in these experiments because they are a popular model organism in behavioral chronobiology research, and are characterized by unusually high levels of voluntary ethanol intake. Relative to controls, ethanol-exposed animals showed attenuation of circadian phase responses and wheel running activity following acute administration of the benzodiazepine, triazolam, a non-photic phase-shifting stimulus. In addition, ethanol-exposed animals displayed reduced phase advances, but normal phase delays, in response to brief light pulses. While the mechanisms underlying these effects remain to be elucidated, we hypothesize that ionotropic GABA and glutamate receptors may be involved, since these proteins serve as important targets for the neurobiological effects of ethanol, and are also known to be critically involved in the modulation of photic and non-photic circadian phase responses.