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Biomedical subjects

S M Armstrong

Publications and source records attributed to S M Armstrong.

54 records · Page 3Linked to original sources

Human melatonin suppression by light is intensity dependent.

Five intensities of artificial light were examined for the effect on nocturnal melatonin concentrations. Maximum suppression of melatonin following 1 hr of light at midnight was 71%, 67%, 44%, 38%, and 16% with intensities of 3,000, 1,000, 500, 350, and 200 lux (lx), respectively. In contrast to some previous reports, light of 1,000 lx intensity was sufficient to suppress melatonin to near daytime levels, and intensities down to 350 lx were shown to significantly suppress nocturnal melatonin levels below prelight values. On the basis of these data, it is suggested that when examining the melatonin sensitivity of patient groups (such as bipolar affective disorders) to artificial light, an appropriate light intensity should be established in each laboratory. Light of less intensity (e.g., 200-350 lx) may be more suitable to dichotomize patient groups from control subjects.

Adult↗

Effect of ovariectomy and estradiol on unity of female rat circadian rhythms.

Sixteen rats were ovariectomized and given either a 1-cm implant of crystalline estradiol-17 beta (eight rats) or an empty implant (eight rats). A further six rats were sham ovariectomized and given empty implants, and eight rats were left unoperated. The rats were exposed to 70 days of constant dim light (LL) with a maximum illumination level of 20 lx, and circadian running and drinking rhythms were monitored. In LL, both the running and drinking activity rhythms of the ovariectomized, blank-implanted rats became markedly disrupted, whereas unoperated and sham-operated rats maintained unified rhythms. Estradiol-implanted rats developed fewer rhythm desynchronies, and the majority displayed a single band of free-running activity. Rather than being arrhythmic, the activity of the LL-exposed ovariectomized rats appeared to contain several free-running components. Thus these data are consistent with the concept of a multioscillatory basis to the circadian system and support a role for the ovary and its hormone estradiol in the maintenance of coherence between component oscillators.

Activity Cycles↗

Food-deprivation-induced phase shifts in Sminthopsis macroura froggatti.

Past research has shown that there is a circadian oscillator in laboratory rats that is entrained by restricted feeding schedules. However, in laboratory rats at least, the light-dark (LD) cycle is the dominant zeitgeber in the entrainment of wheel-running activity rhythms. Given that dasyurid marsupials are predominantly carnivorous, the episodic intake of food in the wild and the high nutritive content of that food suggest that food may be an important zeitgeber in these species. Twelve Sminthopsis macroura froggatti were presented with a daily meal at 0900 hr under an LD 12:12 cycle with lights-on at 0600 hr for 37 days. Activity in anticipation of the meal was observed in most animals. Following this, all animals were exposed to periods of 12-18 days ad lib. food interspersed with 3-day periods of deprivation--a technique used previously to demonstrate persistent meal-associated rhythms. The meal-associated activity rhythms previously observed in rats during the 3-day deprivation period were not seen, but the 3-day deprivation period produced large phase-shifts in the activity rhythms of several S.m. froggatti. It is concluded that meal feeding does not dominate the LD cycle in entraining dasyurid marsupials, but that the frequent observation of phase shifts suggests a different and, perhaps, stronger role for food intake in biological rhythmicity than has been observed previously in laboratory rats.

Animals↗

Treatment of seasonal affective disorder with light: preliminary Australian experience.

Six patients with a history of Seasonal Affective Disorder (SAD) were treated with bright artificial light. Patients presented with at least two consecutive years of loss of energy, difficulty in working, loss of interest in activities, difficulty in concentrating, increased somnolence, over-eating (carbohydrate craving) and depressed mood. All received seven consecutive days of full-spectrum bright light with an intensity greater than 2,500 lux at a distance of three feet. Evening exposure for two hours resulted in significant clinical improvement. The main improvements were a return to normal sleeping patterns, a reduction in eating habits, improved energy level, a desire to continue with interests and activities and an improvement in mood. Possible mechanisms for the clinical effects of bright light treatment are discussed.

Australia↗

Reentrainment of rat circadian activity rhythms: effects of melatonin.

Experiments were conducted to determine whether daily melatonin injections could influence reentrainment of circadian locomotor activity rhythms in male Long-Evans rats after phase shifts of the light dark (LD) cycle. When exposed to a 5-h advance of the LD cycle, six out of 15 rats injected daily with melatonin at the new dark onset reentrained by a phase delay of the activity rhythm. The remaining nine melatonin-injected rats and 14 of the 15 control injected rats phase advanced. Daily melatonin injections administered at the old dark onset did not alter direction of reentraining transients but decreased latency to reach steady-state entrainment. In contrast, the effects of melatonin injections given at the end of both the old and new dark periods are difficult to interpret due to the effects of the injection procedure itself at these times. Following an 8-h advance of the LD cycle, all melatonin-injected rats phase advanced while all vehicle and uninjected control rats phase delayed when injections were given at the old dark onset. As has been found in other research areas, the time of day of melatonin administration appears to be a critical factor in its mode of action. It is yet to be established whether these results from the use of pharmacological doses of melatonin are indicative of endogenous melatonin's involvement in the circadian reentrainment mechanism.

Animals↗

Melatonin administration entrains female rat activity rhythms in constant darkness but not in constant light.

In female rats the luteinizing hormone (LH) is timed by the circadian system and is followed by a display of intense, estrogen-induced running behavior. This proestrous running on the night of ovulation can be used as a marker of the estrous cycle. Entrainment of the mammalian circadian system by exogenous melatonin (MT) has been demonstrated only in the activity rhythms of male rats. The present experiments were designed to study the effect of daily MT injections on activity rhythms and proestrous running of female rats in 1) continuous dim white light (LL) and 2) continuous darkness (DD). In LL, MT injections (50 micrograms/kg or 1 mg/kg) had no discernible effect on activity rhythms. In DD, four of the six MT-treated rats (100 micrograms/kg) entrained to the injection, and a fifth animal showed phase advances in its activity rhythm when onset of activity passed through injection time. The sixth animal was not injected with MT at activity onset time. None of the six control animals showed either effect. MT had no effect on the length of the estrous cycle. Thus MT injections can entrain circadian rhythms of activity and proestrous running in female rats in DD but not in LL.

Animals↗

Melatonin rhythm in human plasma and saliva.

Human plasma and saliva were collected at frequent intervals throughout the night and after a nocturnal challenge by exposure to 3,000 lx of light for 1 h in the middle of the night. Melatonin, as measured by radioimmunoassay, was found to correlate highly in plasma and saliva, described by a linear regression equation: y = 55x-2.6 (r = 0.90). The nocturnal melatonin rhythm in saliva was parallel to that observed in plasma. A good correlation was also observed between plasma and salivary melatonin on exposure to light. Melatonin in both fluids showed a significant fall during light exposure. Levels returned to normal nocturnal values within 2 h after returning to darkness. These results indicate that salivary melatonin, although lower than plasma melatonin, may be used as an index of pineal gland release of melatonin. It is suggested that saliva may be useful as a non-invasive technique for obtaining data on melatonin profiles, especially in pilot-test and screening situations.

Adult↗

Effects of daily melatonin injections on activity rhythms of rats in constant light.

Although from pinealectomy studies the pineal body does not appear to participate in the generation of circadian rhythms of mammals, daily injections of the pineal hormone melatonin entrain free-running locomotor activity rhythms of rats in constant darkness. The aim of the present study was to determine whether rats whose circadian activity and drinking rhythms were disrupted in constant light (LL) could be synchronized by daily melatonin administration. Rats were subjected to a regime of gradually increasing photoperiod until they were maintained in LL. Rats whose rhythms became disrupted or showed intact free-running rhythms were injected daily with either melatonin (1 mg/kg) or vehicle (ethanol-saline) solution. Daily melatonin injections either synchronized or partly synchronized disrupted circadian patterns of activity. In contrast to previous findings from experiments conducted in constant darkness, melatonin did not entrain but only partly synchronized intact free-running rhythms. Results are interpreted in terms of melatonin acting on the coupling or phase relationships between oscillators generating circadian locomotor activity rhythms.

Activity Cycles↗

Restricted feeding and circadian activity rhythms of a predatory marsupial, Dasyuroides byrnei.

There is considerable disagreement as to whether food availability entrains circadian activity rhythms in omnivorous laboratory rodents. However, in carnivorous mammals a restricted feeding regime could act as a zeitgeber because the predator should hold a periodism correlated to that of the prey. Nevertheless, a restricted feeding schedule does not dominate the LD cycle for entrainment of circadian activity rhythms of the nocturnal predator Dasyuroides byrnei, nor does it entrain the free-running activity rhythms in DD. Anticipatory wheel running prior to food availability was observed in most animals. Some evidence for weak coupling between LD-entrained and meal-associated oscillators was indicated by occurrences of relative coordination. This species does not appear to have a dominance hierarchy of zeitgebern different to that reported for laboratory rodents. One would have predicted that it would have been ecologically adaptive for cycles of food availability to be more important than the LD cycle in this species.

Animals↗

Entrainment of rat circadian rhythms by daily injection of melatonin depends upon the hypothalamic suprachiasmatic nuclei.

Although pinealectomy has little effect on the generation of circadian rhythmicity by mammals, daily injections of the pineal hormone melatonin entrain free-running rats [30]. The present study was designed to determine if known components of mammalian circadian organization were necessary for melatonin entrainment. Rats received either lesions to the suprachiasmatic nuclei (SCN), sham-lesions or neurotoxic lesions to brain catecholamines or serotonin. They were then allowed to free-run in constant dim red light (DD) before each received daily injections of either 1 mg/kg melatonin or ethanol:saline vehicle for 90 days. They were allowed to free-run for 30 days afterwards. Rats which received sham-lesions or neurotoxic lesions entrained to melatonin injections but not to vehicle. Rats which received complete SCN lesions were unaffected by melatonin or vehicle. These data suggest that the behavioral effects of melatonin, like those on reproduction in seasonally breeding mammals, depend upon an intact circadian system and the SCN.

Animals↗

Dose-dependent entrainment of rat circadian rhythms by daily injection of melatonin.

Previous work in our laboratory has shown that daily injection of large doses of the pineal hormone melatonin entrains the free-running locomotor rhythms of rats held in constant darkness and synchronizes the disrupted patterns of rats maintained in constant bright light. The present experiments determined the dose-response characteristics of entrainment to daily melatonin injections and made preliminary biochemical estimates of blood melatonin levels and half-lives after two critical doses of the hormone. The data indicated that the median effective dose for melatonin as an entraining agent in free-running rats was 5.45 +/- 1.33 micrograms/kg, considerably lower than doses previously employed and lower than doses employed in reproductive and metabolic studies in rats and hamsters. The data further indicated that the response to melatonin was quantal; rats either entrained to melatonin or they did not. No "partial entrainment" was evident, nor were there differences in phase angle, activity, or period among all effective doses. Biochemical estimates of blood melatonin after either 1 mg/kg or 1 microgram/kg of melatonin indicated that all effective doses resulted in supraphysiological levels of blood melatonin, although doses of 1 microgram/kg resulted in blood levels that were within one order of magnitude of normal nighttime values. Together, the data suggest that the rat circadian system is sensitive to the pineal hormone melatonin at or below doses required to effect rodent reproduction. Whether this sensitivity reflects a role for the pineal gland in rat circadian organization, however, still remains to be determined.

Animals↗

Synchronization of mammalian circadian rhythms by melatonin.

While pinealectomy (Px) has little effect on mammalian circadian rhythms, daily injections of the pineal hormone melatonin in rats have profound effects. These can be classified according to their effects under three categories of desynchronization: external desynchronization, internal desynchronization and phase-shift of the zeitgeber (Aschoff, 1969). Externally desynchronized rats, free-running in constant darkness (DD), can be entrained to a 24-hour regime of melatonin injection. Entrainment depends upon the suprachiasmatic nuclei (SCN) since lesions to the SCN prevent it. Although no animal model for internal desynchronization exists, rats whose circadian rhythms are disrupted or arrhythmic in constant light (LL) are synchronized by daily melatonin injection, and the rate and direction of responses to phase-shift of the zeitgeber can be altered with daily melatonin administration. These and other results suggest melatonin may be useful therapeutically for such human desynchronizations as jet-lag and shiftwork, and preliminary data using human subjects are presented.

Adult↗

Melatonin administration: effects on rodent circadian rhythms.

Previous research has demonstrated a lack of effect of pinealectomy upon the generation of rodent circadian activity rhythms and only a subtle effect upon their reentrainment after phase-shifts of the light-dark cycle. In contrast, our pharmacological studies on melatonin indicate that the pineal gland may be more important than hitherto believed. The main outcome of a preliminary pilot experiment on the effect of daily injections of melatonin, arginine vasotocin, melanocyte-stimulating hormone and a beta-blocker on rat free-running activity rhythms in constant darkness was that melatonin appeared to have entrainment properties. This was clearly demonstrated in a second experiment although entrainment did not occur until the onset of the activity rhythm coincided with the daily injection. In contrast, when melatonin was administered ad lib, in the drinking water to six rats housed in constant dim light, there was apparently a lengthening of the free-running period. The effects of 17 days of melatonin injections given at four different times of day to different groups of rats on re-entrainment of activity rhythms after a 5 h phase-advance of darkness were assessed. Results were confounded by the response of some control rats. However, after an 8 h advance of darkness and daily injection at the time of day of the previous dark onset, melatonin-injected rats phase-advanced, whereas vehicle-injected and uninjected control rats phase-delayed. Thus melatonin can alter the direction, but not necessarily the rate, of re-entrainment. The relevance of some of these findings with pharmacological doses of melatonin to the function of endogenous melatonin is discussed.

Animals↗

Effects of acute food and/or water deprivation on muricide.

The present experiment was designed to test certain predictions derived from models of interactions between muricide and appetitive behaviors proposed earlier by Russell and Singer [8,9]. One of the major features of the models centered on whether the two types of behavior are inevitably related. The general design of the present experiment involved testing for muricide either (a) after deprivation of food and/or water or (b) at times during the normal diurnal cycle when the two consummatory responses were at their minima and maxima. Deprivation and testing for muricide were limited to a single episode in order to eliminate confounding effects of repeated deprivations and of repeated exposures to prey. Periods of acute deprivation ranging from 5.5 to 22.0 hr did not induce significant quantitative changes in muricidal behavior. However, muricide and the appetitive behaviors did co-vary under conditions associated with the normal diurnal cycle. Comparing the present results with findings from experiments using repeated deprivation leads to the suggestion that covariation of appetitive and muricidal behaviors is not an innate characteristic, but rather is acquired through processes of learning. Present results further suggest that each of the two types of behavior has its own physiological substrate which can be modified independently, but also may be activated concomitantly by a common set of antecedent conditions.

Aggression↗

Melatonin, cortisol and prolactin response to acute nocturnal light exposure in healthy volunteers.

An investigation of the cortisol and prolactin responses accompanying acute melatonin suppression by light (600 lux) in humans is described. Light given from midnight to 0300h suppressed nocturnal plasma melatonin concentrations by 65%. Despite this significant suppression of melatonin, no significant effect on plasma cortisol or prolactin concentrations was observed. These data support recent studies which argue that, if there is a relationship between melatonin, the hypothalamo-pituitary, and the hypothalamo-pituitary-adrenal axis in humans, it is neither direct nor simple.

Adult↗