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Biomedical subjects

F W Turek

Publications and source records attributed to F W Turek.

At least 145 records · Page 8Linked to original sources
PubMed1989

Effects of stimulated physical activity on the circadian pacemaker of vertebrates.

A dogma in the field of circadian rhythms is that in order to keep accurate time, pacemakers that generate such rhythms must be relatively independent of changes in the external and internal environment. While it is true that the period of circadian oscillators is conserved within a narrow range, regardless of alterations in the external and internal environment, numerous perturbations have now been found that can change the period and/or induce a phase shift in circadian pacemakers. Many of these perturbations also alter the overall level of activity and/or metabolic state of the organism. In 1960, Aschoff suggested that alterations in the "level of excitement" may induce changes in circadian clocks. Although little attention has been given to this hypothesis over the past three decades, recent findings support its validity and open new avenues for studying the function and organization of circadian clock systems.

Animals↗
PubMed1988

A benzodiazepine antagonist, Ro 15-1788, can block the phase-shifting effects of triazolam on the mammalian circadian clock.

A single injection of the short acting benzodiazepine, triazolam, can induce permanent phase advances as well as phase delays in the onset of the circadian rhythm of wheel running behavior in hamsters free-running under constant environmental conditions. If the phase shifting effects of triazolam on the circadian system are mediated through the benzodiazepine-GABA receptor complex, then it should be possible to block these effects with RO 15-1788, a selective benzodiazepine antagonist, which acts at the benzodiazepine-GABA receptor level. To test this hypothesis, hamsters free running in constant light received an intraperitoneal injection of various doses of Ro 15-1788 15 min before a single i.p. injection of 0.5 mg of triazolam. This dose of triazolam is known to induce maximal phase shifts in the circadian rhythm of wheel running behavior in hamster. Treatment with Ro 15-1788 totally blocked both the phase advancing and phase delaying effects of triazolam, while the administration of Ro 15-1788 alone did not phase shift the activity rhythm. These results support the hypothesis that the phase shifting effects of triazolam are mediated through the benzodiazepine-GABA receptor complex. The absence of any phase shifting effects of Ro 15-1788 when delivered alone suggests that Ro 15-1788 has no partial agonist properties in this experimental paradigm.

Animals↗
PubMed1988

Estrous correlated modulations of circadian and ultradian wheel-running activity rhythms in LEW/Ztm rats.

Estrogen treatment alters the expression of ultradian activity rhythms in male and female LEW/Ztm rats. This finding raises the possibility that the expression of ultradian rhythms may vary on different days of the estrous cycle. To test this hypothesis, we recorded the circadian and ultradian wheel-running activity rhythms of entrained (LD 12:12) and free-running sexually mature LEW/Ztm females during their 4- or 5-day estrous cycle. The mean daily activity, the duration of activity, the circadian period of activity, and the occurrence of ultradian rhythms differed significantly among the days of the estrous cycle. In LD 12:12, the phase angle difference between the beginning of activity and light offset varied reliably in 5-day cycling animals. The highest daily mean of activity, the longest duration, and the shortest circadian period length were observed on the day of estrus in both entrained and free-running animals. The day of estrus was characterized by a constant high level of activity throughout the activity phase, while the days following ovulation showed a bi- or trimodal activity pattern. Power spectrum analysis revealed significant ultradian components for the days of metestrus and diestrus, but only circadian components for the days of proestrus and estrus. These results were interpreted as indicating that endogenous changes in circulating hormone levels can induce changes in the ultradian and circadian patterns of wheel-running activity in LEW/Ztm rats.

Animals↗
PubMed1988

Manipulation of a central circadian clock regulating behavioral and endocrine rhythms with a short-acting benzodiazepine used in the treatment of insomnia.

Abnormal circadian rhythms have been linked to at least some forms of depression and to disturbances in the sleep-wake cycle. In addition, mental and physical disorders that are associated with rapid travel across time zones (i.e. the jet-lag syndrome) and with rotating shift-work schedules, are thought to involve a disruption of normal circadian rhythmicity. It might be possible to alleviate some of the adverse effects of abnormal circadian rhythms if pharmacological agents could be used to manipulate the central circadian pacemaker(s) that regulate these rhythms. Studies in our laboratory indicate that treatment with a short-acting benzodiazepine, triazolam, can induce major shifts in both behavioral and endocrine circadian rhythms in hamsters under a variety of experimental conditions. In the absence of a synchronizing light-dark cycle (i.e. during exposure to constant light or constant dark), single or multiple injections of triazolam can induce a permanent phase shift in both the circadian rhythm of locomotor activity and the circadian rhythm of pituitary LH release. In addition, repeated daily injections of triazolam can alter the entrained phase relationship of the circadian activity rhythm to a fixed light-dark cycle, and following a shift in the light-dark cycle, a single injection of triazolam can facilitate the time it takes for the activity rhythm to be resynchronized to the new lighting schedule. Thus, triazolam, or drugs with similar phase-shifting effects on the mammalian circadian system, might be useful in the treatment of various physical and mental illnesses that have been associated with a disorder in circadian time-keeping in humans.

Animals↗
PubMed1988

Pharmacological manipulation of the mammalian circadian clock: implications for the control of seasonal reproductive cycles.

Although artificial control of the light cycle can be used to regulate the seasonal reproductive cycle of many animals under laboratory conditions, such regulation is often not possible in a standard agricultural environment. An alternative strategy for regulating the seasonal reproductive cycle of photoperiodic animals is to use drugs that either mimic the effects of light on reproductive function or that induce an alteration in the way the circadian clock system is entrained by the light cycle. The ability to use drugs to achieve these objectives has been demonstrated in the laboratory, but it remains to be determined if such an approach can be used to regulate the breeding season of farm animals under normal agricultural conditions.

Animals↗
PubMed1988

Manipulation of the circadian clock with benzodiazepines: implications for altering the sleep-wake cycle.

Abnormal circadian rhythms have been linked to at least some forms of depression and to disturbances in the sleep-wake cycle. In addition, mental and physical disorders associated with rapid travel across time zones (i.e. the jet-lag syndrome) and with rotating shift-work schedules, are thought to involve a disruption of normal circadian rhythmicity. It might be possible to alleviate some of the adverse effects associated with abnormal circadian rhythms if pharmacological agents could be used to manipulate the central circadian pacemaker(s) that regulates these rhythms. Recent findings indicate that treatment with a short-acting benzodiazepine, triazolam, can induce major shifts in the circadian clock of golden hamsters. In the absence of a synchronizing light-dark cycle (i.e. during exposure to constant light or constant dark), a single injection of triazolam can induce a permanent phase shift in the circadian rhythm in locomotor activity. In addition, following a shift in the light-dark cycle, a single injection of triazolam can facilitate the time it takes for the activity rhythm to be resynchronized to the new lighting schedule. Triazolam, or drugs with similar phase-shifting effects on the mammalian circadian system, might be useful in the treatment of various sleep and mental disorders that have been associated with a disorder in circadian time-keeping in humans.

Animals↗
PubMed1988

Effects of melatonin and 6-methoxybenzoxazolinone on photoperiodic control of testis size in adult male golden hamsters.

Consumption of young plants containing 6-methoxybenzoxazolinone (6-MBOA) appears to play an important role in the initiation of reproduction each spring in wild populations of the montane vole. Following its identification, 6-MBOA has been found to stimulate the reproductive system in a number of rodent species, but the mechanism of action remains unknown. The chemical structure of 6-MBOA is similar to melatonin, which, in addition to its well-known antigonadal effects, can exert a progonadal influence under certain experimental conditions. To determine if 6-MBOA might act as a melatonin agonist, four experiments were conducted to compare the effect of these two compounds on testis size in the golden hamster, a rodent whose responses to melatonin are well characterized. 1) Hamsters exposed to 14 h light per day (14L:10D) received a daily injection of melatonin (25.0 micrograms) or 6-MBOA (17.8 micrograms). 2) Hamsters exposed to 6L:18D received Silastic capsules (50 or 200 mm) containing melatonin or 6-MBOA. 3) Hamsters exposed to 6L:18D received chow containing melatonin (21.1 or 42.2 micrograms/gm chow) or 6-MBOA (15.0 or 30.0 micrograms/gm). 4) Hamsters exposed to 6L:18D received drinking water containing melatonin (15.5 micrograms/ml) or 6-MBOA (11.0 micrograms/ml). Testis widths were determined at 2--3 week intervals, and after 66-73 days testes were removed and weighed. Melatonin significantly influenced testis size in each experiment, but treatment with 6-MBOA had no effect in any of these experimental paradigms, indicating that 6-MBOA does not act as a melatonin agonist in the hamster. However, these results indicate that the consumption of melatonin (and presumably melatonin agonists) could serve as an environmental stimulus for reproductive activity.

Animals↗
PubMed1988

Inhibitor of protein synthesis phase shifts a circadian pacemaker in mammalian SCN.

The suprachiasmatic nucleus (SCN) of the hypothalamus contains a circadian pacemaker that regulates many circadian rhythms in mammals. Experimental work in microorganisms and invertebrates suggests that protein synthesis is required for the function of the circadian oscillator, and recent experiments in golden hamsters suggest an acute inhibition of protein synthesis can induce phase shifts in a mammalian circadian pacemaker. To determine whether protein synthesis in the SCN region is involved in the generation of circadian rhythms in mammals, a protein synthesis inhibitor, anisomycin, was microinjected into the SCN region, and the effect on the circadian rhythm of locomotor activity of hamsters was measured. A single injection of anisomycin into the SCN region induced phase shifts in the circadian activity rhythm that varied systematically as a function of the phase of injection within the circadian cycle. These results suggest that protein synthesis may be involved in the generation of circadian rhythms in mammals and that the anatomic site of action of anisomycin is within the hypothalamic suprachiasmatic region.

Animals↗
PubMed1988

Transfer from long to short days reduces the frequency of pulsatile luteinizing hormone release in intact but not in castrated male golden hamsters.

In the golden hamster, prolonged exposure to short days (i.e. less than 12.5 h of light/day) induces testicular regression that has usually, but not always, been reported to be accompanied by a decrease in mean serum luteinizing hormone (LH) levels. As LH appears to be released in a pulsatile pattern in most mammalian species, we hypothesized that individual variations in serum LH levels over time may obscure significant changes in pituitary LH release in hamsters exposed to short photoperiods. Therefore, we examined the effects of short day exposure on pulsatile LH release in castrated and intact golden hamsters. Intact and castrated male golden hamsters were maintained on long days (light:dark 14:10 h) or transferred to short days (light:dark 6:18 h). Nine to eleven weeks after transfer, animals from all four groups were fitted with intra-atrial cannulas and bled at 10-min intervals for 6 h. Exposure to short days inhibited LH release in the intact male hamsters. All 6 of the males maintained on long days had pulsatile LH release while only 1 of the 4 intact males maintained on short days showed a pulse of LH during the 6-hour bleeding session. All of the castrates on short days had pulsatile patterns of LH release that were similar in amplitude and frequency to those of the castrates on long days. Castrates on long days had significantly greater LH pulse frequency and amplitude than intacts on long days. From these data we conclude that the pulsatile nature of pituitary LH release in the golden hamster mandates frequent sampling over several hours for accurate determination of serum LH levels and for determining the effects of photoperiod on pituitary gonadotropin release.

Animals↗
PubMed1988

The circadian rhythm of LH release can be shifted by injections of a benzodiazepine in female golden hamsters.

Three daily injections of the short-acting benzodiazepine, triazolam, induced pronounced phase shifts in the onset of both the circadian surge in pituitary LH release and the circadian rhythm of locomotor activity in ovariectomized hamsters treated with estrogen. Both the magnitude and the direction of the phase shifts in these two rhythms were similar. These results indicate that a master circadian clock underlying diverse behavioral and endocrine rhythms can be reset by treatment with triazolam.

Animals↗
PubMed1988

The importance of follicle-stimulating hormone in the initiation of testicular growth in photostimulated Djungarian hamsters.

Juvenile male Djungarian hamsters (Phodopus sungorus sungorus) exhibit rapid and robust increases in both serum FSH and testicular weight within 1 week of transfer from nonstimulatory short days to stimulatory long days, while serum LH levels rise little or not at all during this same time period. Two experiments were performed to determine whether the rapid increase in serum FSH is responsible for the initial increase in testis weight. In the first study, the rapid increase in serum FSH levels, which normally occurs in response to photostimulation, was suppressed by twice daily injections of porcine follicular fluid, a substance known to contain the FSH-suppressing protein inhibin. Suppression of serum FSH levels during the 7 days of photostimulation resulted in an inhibition of testicular growth. In the second study, young male Djungarian hamsters housed in a short photoperiod were implanted with Alzet minipumps containing ovine (o) FSH in order to experimentally raise serum FSH levels. Another group of animals exposed to short days received minipumps containing oLH. Administration of oFSH, but not oLH, induced testicular growth comparable to that in animals transferred to a stimulatory photoperiod. Furthermore, administration of oFSH was able to overcome the inhibitory effects of porcine follicular fluid on the testes. These results suggest that the rapid increase in serum FSH after photostimulation is the primary signal for initiating testicular development in this seasonally breeding species.

Animals↗
PubMed1987

Phase shifts in the circadian activity rhythm induced by triazolam are not mediated by the eyes or the pineal gland in the hamster.

A single injection of the benzodiazepine triazolam, which is though to act by potentiating the effects of the neurotransmitter gamma-aminobutyric acid (GABA), can induce permanent phase shifts in the circadian rhythm of locomotor activity of hamsters. Occurrence of GABA immunoreactivity and benzodiazepine receptors in the retina, which contains photoreceptors that relay synchronizing light-dark information to the mammalian circadian system, raises the possibility that triazolam may influence circadian rhythmicity via an action on the retina. However, the phase shifting effects of triazolam on the activity rhythm were unaffected by blinding: the direction and the magnitude of the phase shifts were similar in blind hamsters and in sighted hamsters maintained in constant darkness. Furthermore, no change in response to triazolam was observed in hamsters studied through 84 days after blinding. In addition, benzodiazepine binding sites have been found in the mammalian pineal gland, which has also been implicated in circadian rhythmicity. Therefore, its possible involvement in mediating the phase advancing effects of triazolam on the circadian clock has also been tested: the response was similar in blind and blind-pinealectomized animals. These results indicate that the effects of triazolam on the circadian clock are not mediated by the eyes or the pineal gland.

Animals↗
PubMed1987

Dose response curve for the phase-shifting effect of triazolam on the mammalian circadian clock.

A dose response curve for the phase shifting effect of triazolam, a short-acting benzodiazepine commonly prescribed for the treatment of insomnia, on the circadian rhythm of locomotor activity was measured for the golden hamster. A single intraperitoneal injection of triazolam six hours before the onset of wheel-running activity induced a dose-dependent phase advance in the rhythm. A maximum phase advance, which averaged about 100 minutes, was observed in animals injected with 0.5 to 5.0 mg of triazolam. The use of drugs which promote sleep, and induce phase shifts in a central circadian clock, could be important in the treatment of sleep disorders associated with disrupted schedules and of mental and physical disorders associated with abnormal circadian rhythmicity.

Animals↗
PubMed1987

Anisomycin, an inhibitor of protein synthesis, perturbs the phase of a mammalian circadian pacemaker.

Administration of the protein synthesis inhibitor, anisomycin, induced both advance and delay phase-shifts in the circadian rhythm of locomotor activity in hamsters maintained in constant darkness. The magnitude and direction of the phase shift was dependent on the circadian time of drug treatment. A second protein synthesis inhibitor, cycloheximide, also induced phase-shifts in the circadian rhythm of activity, while two drugs which mimic some of the side effects of protein synthesis inhibitors had no significant effect on the activity rhythm. The phase-response curve generated by anisomycin injections in the hamster is similar to the response curves that have been measured for protein synthesis inhibitors in micro-organisms and invertebrates. Thus, the biochemical mechanisms generating circadian oscillations in mammals may share common features with those found in very distantly related phylogenetic groups.

Animals↗
PubMed1987

A cholinergic antagonist, mecamylamine, blocks the phase-shifting effects of light on the circadian rhythm of locomotor activity in the golden hamster.

Despite the well known role of the light-dark cycle in the entrainment of circadian rhythms, very little is known about the neurochemical events that mediate the effects of light on the mammalian circadian clock. Recent anatomical and pharmacological data support the hypothesis that acetylcholine may be involved in relaying light-dark information from the retina to, or within, the circadian clock of rodents. If acetylcholine is required for this response, it should be possible to block the phase-shifting effects of a light pulse by blocking cholinergic neurotransmission. To test this possibility, hamsters free-running in constant darkness received an intraventricular injection of the anticholinergic drug, mecamylamine (450 micrograms), 10 min before being exposed to a 5-min pulse of light known to induce sub-maximal phase shifts in the circadian rhythm of wheel-running behavior. Compared to vehicle-injected control animals, mecamylamine treatment blocked or reduced both the phase-advancing and phase-delaying effects of light. These results support the hypothesis that acetylcholine is involved in mediating the phase-shifting effects of light on the mammalian circadian clock.

Animals↗
PubMed1987

Circadian and seasonal control of neuroendocrine-gonadal activity.

A circadian clock(s) located in the suprachiasmatic nucleus (SCN) of the hypothalamus plays an important role in regulating the timing of pituitary gonadotropin release in many mammalian species. The results from studies involving two unusual experimental paradigms are presented to demonstrate a role for this circadian clock in the regulation of the timing of the preovulatory LH surge in the golden hamster as well as in the measurement of the seasonal change in day length in the Djungarian hamster; information which is used in the regulation of neuroendocrine-gonadal activity on a seasonal basis. The data also demonstrate that the circadian rhythm of locomotor activity can be used as a "marker" rhythm for the clock involved in both ovulatory and seasonal cycles in hamsters.

Activity Cycles↗
PubMed1987

Photoperiodic response in the male laboratory rat.

Normally photoperiodic laboratory rats can be induced to respond reproductively to a change in the length of the day by various experimental manipulations. One such paradigm that results in significant gonadal regression involves the treatment of rats with exogenous testosterone during exposure to short days. Studies were undertaken to assess various aspects of this model system including 1) the testicular response of testosterone-treated rats exposed to various photoperiods, 2) the time course for testicular regression under a short photoperiod, and 3) the role of the pineal gland as a mediator of the effects of day length on the neuroendocrine-gonadal axis. Photoperiods ranging in length from 2 to 22 h/24 h had no effect on testicular size in untreated rats. In contrast, while near normal testicular weights were maintained in laboratory rats treated with testosterone and exposed to 10 or more h of light per day, testicular regression occurred in rats implanted with testosterone-filled capsules and exposed to photoperiods of 8 or fewer h of light per day. Maximal testicular regression was reached in about 9 wk in testosterone-treated rats exposed to 6L:18D. Removal of the pineal gland totally blocked the inhibitory effects of exposure to short day lengths in testosterone-treated rats. These studies define some of the characteristics of an extant, but dormant, system for photoperiodic time measurement in the common laboratory rat and implicate a role for the pineal gland in this system. These experiments offer evidence that neuroendocrine factors that regulate continuous vs. seasonal reproductive patterns are malleable. Such flexibility in the photoperiodic response may also contribute to the evolution of seasonal to non-seasonal species and vice versa.

Animals↗