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Biomedical subjects

F W Turek

Publications and source records attributed to F W Turek.

At least 127 records · Page 7Linked to original sources
PubMed1991

Phase-shifting effects of acute increases in activity on circadian locomotor rhythms in hamsters.

Experiments were conducted in golden hamsters to examine the relationship between induced acute increases in locomotor activity and phase shifts in the circadian clock underlying the rhythm of activity. Injections of the short-acting benzodiazepine triazolam (TZ) 6 h before the onset of activity resulted in an acute increase in activity and a phase advance in the rhythm of activity; injections of TZ induced larger phase shifts in animals housed without running wheels than in those housed with wheels. Transfer to a cage with access to a running wheel for 1 h at different circadian times induced large phase advances (mean of 2 h) and small phase delays depending on the circadian time of transfer. Maximal mean phase advances resulted when animals were transferred to a cage with wheel 3 h before activity onset, and at this circadian time there was a significant correlation between the magnitude of the phase shift and the amount of increase over baseline activity for the first hour after transfer. These results indicate that access to a running wheel in animals housed without wheels can be a significant phase-shifting stimulus to the circadian clock and that the phase shifts induced by injection of TZ or transfer to a new cage with wheel are related to the activity state of the animal or to the amount of locomotor activity that is induced at particular times.

Animals↗
PubMed1991

Photoperiodic differences in in vitro pituitary gonadotropin basal secretion and gonadotropin-releasing hormone responsiveness in the golden hamster.

In order to examine pituitary gonadotropin secretion and responsiveness to GnRH after photic-induced changes in reproductive condition, an in vitro pituitary perifusion system was established for male golden hamster tissue. Anterior pituitaries from adult males which had been maintained on 14 h light:10 h dark (long days) or 6 h light:18 h dark (short days) for 10 weeks were perifused using an Acusyst perifusion system. Perfusates from unstimulated tissue (basal secretion) and from tissue stimulated with hourly pulses of GnRH (25, 50, or 100 ng/ml) were assayed for LH and FSH by RIA. Tissue from short-day animals had lower basal LH secretion than tissue from long day animals, but there were no significant photoperiodic differences for GnRH-stimulated LH secretion. In contrast, there were no photoperiodic differences in basal FSH secretion, but tissue from short-day animals secreted more FSH than tissue from long-day animals when stimulated with GnRH. Bioactivity of a small number of perfusate samples was assessed using in vitro rat granulosa cell and mouse Leydig cell assays for FSH and LH, respectively, and did not show any photoperiodic differences in LH or FSH bioactivity for GnRH-stimulated tissue. These studies indicate that the pituitaries of gonadally regressed hamsters are capable in vitro of responding to GnRH with similar or greater levels of gonadotropin release compared to pituitaries from animals with functional gonads. Therefore, it appears that the lowered serum gonadotropin levels seen in vivo in gonadally regressed animals are not due to a reduction in intrinsic pituitary sensitivity to GnRH.

Animals↗
PubMed1991

Pulsatile luteinizing hormone responses to intermittent N-methyl-D,L-aspartate administration in hamsters exposed to long- and short-day photoperiods.

Hamsters exposed to short-day photoperiods (6-h light, 18-h darkness) develop a reversible inhibition of the reproductive axis which includes decreased LH pulse frequency, decreased FSH and testosterone levels, testicular regression, and presumably, decreased luteinizing hormone-releasing hormone (LHRH) release. The decrease in LHRH release could reflect a decrease in the ability of LHRH neurons to release the decapeptide in response to intermittent neuronal excitation. To analyze this possibility, the LHRH secretagogue, N-methyl-D-aspartate (NMA) was used to estimate relative releasability of endogenous LHRH pulses in hamsters exposed to long- and short-day photoperiods. Long-day (LD) or short-day (SD) hamsters were fitted with indwelling atrial catheters 2 days before experimentation. During 5-h sampling sessions (1300-1800 h), blood was withdrawn at 10-min intervals. In initial experiments, a NMA dose-response analysis revealed that 10 and 20 mg/kg NMA but not 2.5 and 5 mg/kg NMA, produced significant, dose-related LH responses in LD hamsters. Treatments with LHRH antagonist 4 h prior to NMA treatment completely blocked LH responses. The 10 mg/kg NMA dose was then used to directly compare LHRH responsiveness in LD and SD hamsters. NMA injections were administered to groups of LD and SD hamsters after hours 1, 2, 3, and 4 of sampling. In LD hamsters, LH responses to the first NMA pulse (2.65 +/- 0.09) were followed by diminishing responses to the second, third, and fourth NMA pulses (1.22 +/- 0.50, 1.22 +/- 0.43, and 1.15 +/- 0.42). By contrast, initial LH responses in SD hamsters (1.61 +/- 0.31) were followed by even more robust LH responses to the second, third, and fourth NMA challenges (2.89 +/- 0.34, 3.08 +/- 0.59, 2.65 +/- 0.32). Although LH responses to the first NMA pulse were slightly less in SD vs. LD animals, responses to all subsequent injections were actually greater in SD hamsters vs. their LD counterparts. Injections of 20 ng/kg LHRH in SD hamsters produced LH responses similar to those evoked by NMA. The same LHRH dose also produced continued, robust LH responses in LD hamsters, indicating that decrements in response to NMA were not due to diminished pituitary responsiveness. These results suggest that 1) the stimulatory actions of NMA are mediated by LHRH, 2) exposure to short days does not decrease the responsiveness of LHRH neurons to NMA, and 3) successive NMA challenges produce diminishing LH responses in LD hamsters, but not in SD hamsters.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Bicuculline and picrotoxin block phase advances induced by GABA agonists in the circadian rhythm of locomotor activity in the golden hamster by a phaclofen-insensitive mechanism.

Permanent phase shifts in the free-running rhythm of locomotor activity of the golden hamster were induced with microinjections of the gamma-aminobutyric acid (GABA) agonists muscimol or baclofen in the hypothalamic suprachiasmatic nuclei. Muscimol and baclofen exhibit relatively high binding affinities for GABAA and GABAB receptors, respectively. Microinjections of the GABA antagonists, bicuculline methobromide or picrotoxinin, thought to block the actions of GABA at GABAA receptors, could block phase shifts induced by muscimol but not the benzodiazepine, triazolam. Microinjections of the postsynaptic GABAB receptor antagonist phaclofen, which blocks the actions of GABA at postsynaptic but not at presynaptic GABAB receptor sites, did not block the phase-shifting actions of either muscimol or baclofen. GABAergic antagonists when given alone did not induce phase shifts. Collectively, these studies indicate that when activated by exogenous GABAergic agents, a GABAergic system associated with both GABAA and GABAB receptors exists as a neural regulatory mechanism that can reset the mammalian circadian clock. However, GABAergic synaptic pathways may not be normally involved in the circadian timing system.

Animals↗
PubMed1990

Photic threshold for stimulation of testicular growth and pituitary FSH release in male Djungarian hamsters.

While the effects of photoperiod on neuroendocrine-gonadal activity have been extensively studied in a number of species, surprisingly little information concerning the quantitative aspects of light regulating reproductive activity is available. In the present experiment, Djungarian hamsters were exposed to two 10 min pulses of light per day and the light irradiance was systematically varied to determine the threshold for photostimulation by white light. After 10 days testes weight and serum follicle-stimulating hormone (FSH) levels were determined. The data indicate that the irradiance threshold necessary for induction of significant increases of both serum FSH levels and testes weight lies between 0.1 and 0.34 microW/cm2 for 10 min pulses of light. These results demonstrate a strong correlation between the effects of light on serum FSH levels and testes weight and provide the first quantitative assessment of the irradiance threshold for light involved in photoperiodic stimulation of the hypothalamic-pituitary gonadal axis of a mammalian species.

Animals↗
PubMed1990

Daily injections of triazolam induce long-term changes in hamster circadian period.

Previous experiments in hamsters indicate that daily injections of the short-acting benzodiazepine, triazolam, can entrain the free-running circadian activity rhythm to the period of the injections and that, after discontinuation of triazolam injections, the period of the free-running activity rhythm remains close to that of the previous injection schedule for 20-50 cycles. In this paper, we extend these findings and demonstrate that 1) long-term treatment with triazolam can induce aftereffects on the period of the circadian clock underlying the activity rhythm that can last for up to 100 days, 2) triazolam-induced changes in period can lead to a loss of effect of daily injections of triazolam which can be restored if the time of injection is altered, and 3) chronic treatment with triazolam also alters the period of the circadian clock in animals entrained to a light-dark cycle, and such changes in period alter the phase relationship between the circadian clock and the entraining light-dark cycle.

Activity Cycles↗
PubMed1990

Effects of the short-acting benzodiazepine triazolam, taken at bedtime, on circadian and sleep-related hormonal profiles in normal men.

Studies in rodents have shown that triazolam, a commonly used hypnotic, may shift circadian rhythms, with the direction and magnitude of the phase-shifts being dependent on the time of drug administration. To determine whether benzodiazepine, taken at standard bedtime, modifies the amount and/or temporal organization of hormonal secretion, six normal men were studied during basal conditions and on the first and third days of treatment with 0.5 mg triazolam. In each study, sleep was polygraphically monitored and plasma cortisol, growth hormone (GH), melatonin, and prolactin (PRL) (i.e., hormones influenced by circadian rhythmicity and/or sleep) were measured at 20-min intervals for 24 h. The sleep latency and the number and duration of awakenings were reduced during triazolam treatment as compared to baseline conditions. The only alteration of sleep architecture was a partial suppression of stages III + IV (SW) in late sleep. Triazolam did not affect the mean cortisol and melatonin levels or the total amount of GH secreted over the 24-h span. The circadian timings of the onsets of cortisol and melatonin secretions were essentially unaltered. The nocturnal rise of melatonin was prolonged by 45 to 60 minutes. Sleep-associated GH release was not modified by triazolam. Sleep-associated PRL secretion persisted, but in half of the nights studied was enhanced almost threefold. This effect of the drug on nocturnal PRL secretion was not specific to either the first or the third night of treatment, nor was it specific to certain subjects. Irrespective of the magnitude of the nocturnal elevation, morning PRL levels were slightly but consistently higher after triazolam treatment than under basal conditions. Normal PRL levels resumed around noon. In conclusion, administration of 0.5 mg triazolam at normal bedtime (2230) for three consecutive days may induce a transient hyperprolactinemia, but does not abolish sleep-related hormone secretion and does not affect the timing of endocrine events controlled by the circadian clock. These findings are consistent with studies in hamsters where treatment with triazolam in the early subjective night was also without effect on the rodent circadian clock.

Animals↗
PubMed1989

Carbachol phase shifts the circadian rhythm of locomotor activity in the Djungarian hamster.

The effects of light on the circadian system may involve the neurotransmitter acetylcholine (ACh). The purpose of the present study was to determine whether carbachol, a cholinergic agonist, mimics the phase-shifting effects of light on the circadian rhythm of locomotor activity (CRLA) in the Djungarian hamster. Phase response curves (PRCs) were measured for blind animals injected intracerebroventricularly with either vehicle or carbachol at different circadian times. Carbachol produced significant phase delays in the CRLA when administered at circadian time (CT) 12-16 and small, but significant phase advances when given at CT 8. No consistent phase shifts were observed in response to carbachol injections at other circadian times. Phase shifts produced by carbachol injections at CT 8 and 12 were similar for both sighted and blind animals. Light pulses to sighted hamsters produced phase advances at CT 20 and phase delays at CT 12. Both the carbachol PRC and the PRC for light pulses in the Djungarian hamster have phase delay regions in the early subjective night. However, these two PRCs have different phase advance regions. These results indicate that carbachol mimics some of the effects of light on the circadian system in the Djungarian hamster and support the hypothesis that cholinergic mechanisms may play a role in mediating some of the phase-shifting effects of light on the circadian clock of mammals.

Animals↗
PubMed1989

Phase shifting the circadian clock with cycloheximide: response of hamsters with an intact or a split rhythm of locomotor activity.

Systemic administration of the protein synthesis inhibitor, cycloheximide, induced both phase advances and phase delays in the circadian rhythm of wheel-running activity in hamsters (Mesocricetus auratus) maintained in constant darkness or constant light. The magnitude and direction of the phase shifts were dependent on the circadian time (CT) of drug treatment. The phase response curves in constant darkness and constant light were of similar general shape, but they differed in the overall mean amplitude of the phase shifts. Maximal phase advances were observed after injections around CT 6-8, maximal delays at CT 0-2. Injections of various doses of cycloheximide at CT 0 induced a dose-dependent phase delay in the rhythm with a maximum delay induced by 10 mg cycloheximide. Injections of cycloheximide in animals with a split activity rhythm caused phase shifts of both components in the same direction (20/39) and in different directions (10/39). The results support the hypothesis that 80S ribosomal protein synthesis plays an important role in the biochemical mechanisms of circadian systems.

Animals↗
PubMed1989

Stimulated activity mediates phase shifts in the hamster circadian clock induced by dark pulses or benzodiazepines.

A number of environmental and pharmacological stimuli capable of inducing phase shifts and/or period changes in the circadian clock of mammals have now been identified. Agents that can alter circadian clocks provide a means for investigating the cellular and neural mechanisms responsible for their generation, regulation and entrainment. Two stimuli that have been used to probe the basis of circadian rhythmicity are pulses of darkness on a background of constant light and injections of short-acting benzodiazepines, such as triazolam. Surprisingly, these two very different stimuli have remarkably similar phase-shifting effects on the circadian clock of hamsters. The observation that a short-term increase in locomotor activity occurs when the circadian activity rhythm of hamsters is shifted by dark pulses or triazolam injections, coupled with the finding that activity bouts themselves are capable of shifting this rhythm, raises the possibility that dark pulses or triazolam alter the circadian clock by inducing acute hyperactivity. Here we demonstrate that the phase-advancing and phase-delaying effects of dark pulses or triazolam on the circadian activity rhythm can be totally suppressed by immobilization of the animals during treatment. These results indicate that behavioural events mediate the phase-shifting effects of both dark pulses and triazolam on the circadian activity rhythm and question present hypotheses regarding the pathways by which light-dark information and pharmacological agents influence circadian pacemakers.

Activity Cycles↗
PubMed1989

Beta-methyl carboline, a benzodiazepine inverse agonist, attenuates the effect of triazolam on the circadian rhythm of locomotor activity.

The benzodiazepine triazolam, the benzodiazepine inverse agonist, beta-methyl carboline (beta-CCM) or both, were administered to adult male hamsters under conditions of constant light. When given alone, triazolam induced phase advances in the circadian activity rhythm of about 90 min, while beta-CCM when given alone, had no effect on phase of the activity rhythm. However, when triazolam and beta-CCM were given at the same time, the magnitude of the phase advances induced by triazolam were attenuated to about 30 min. These data, in conjunction with previous results, provide pharmacological evidence for a GABAergic system involved in the regulation of a central circadian pacemaker.

Animals↗
PubMed1989

Single injections of triazolam, a short-acting benzodiazepine, lengthen the period of the circadian activity rhythm in golden hamsters.

Single injections of the benzodiazepine, triazolam, induce phase shifts and cause a lengthening of the circadian activity rhythm in the golden hamster. The effect of triazolam on period depends on the phase of injection, but is not dependent on the direction of the phase shifts. Triazolam injections caused increases in period that were associated with phase advances as well as phase delays in the activity rhythm. This relationship between triazolam-induced phase shifts and changes in period is different from the relationship between light-induced phase shifts and period changes.

Activity Cycles↗
PubMed1989

Central administration of muscimol phase-shifts the mammalian circadian clock.

The suprachiasmatic nucleus (SCN) of the hypothalamus contains a neural oscillatory system which regulates many circadian rhythms in mammals. Immunohistochemical evidence indicates that a relatively high density of GABAergic neurons exist in the suprachiasmatic region. Since intraperitoneal injections of the benzodiazepine, triazolam, have been shown to induce phase shifts in the free-running circadian rhythm of locomotor activity in the golden hamster, the extent to which microinjections of muscimol, a specific agonist for gamma-aminobutyric acid (GABA), may cause phase-shifts in hamster activity rhythms was investigated. Stereotaxically implanted guide cannulae aimed at the region of the SCN were used to deliver repeated microinjections in individual animals. A phase-response curve (PRC) generated from microinjections of muscimol revealed that the magnitude and direction of permanent phase-shifts in the activity rhythm were associated with the time of administration. The PRC generated for muscimol was characterized by maximal phase-advances induced 6 h before activity onset and by maximal phase-delays which occurred 6 h after activity onset. The PRC for muscimol had a shape similar to a PRC previously generated for the short-acting benzodiazepine, triazolam. Single microinjections of different doses of muscimol given 6 h before activity onset induced phase-advances in a dose-dependent fashion. Histological analysis revealed that phase shifts induced by the administration of muscimol were associated with the proximity of the injection site to the SCN area. These data indicate that a GABAergic system may exist within the suprachiasmatic region as part of a central biological clock responsible for the regulation of the circadian rhythm of locomotor activity in the golden hamster.

Animals↗
PubMed1989

Midazolam, a short-acting benzodiazepine, resets the circadian clock of the hamster.

Treatment with the short-acting benzodiazepine, triazolam, has been found to induce changes in both behavioral and endocrine circadian rhythms in hamsters. The objective of this study was to determine if these effects of triazolam could be generalized to other short-acting benzodiazepines. Therefore, the effects of midazolam on the biological clock of the hamster were examined in detail. A phase-response curve and a dose-response curve were measured to determine the effects of a single intraperitoneal injection of midazolam on the circadian clock of hamsters free-running in constant light. Midazolam injections produced maximal phase advances at circadian time (CT) 6 and 9 and maximal phase delays at CT 15 and 21. Doses of 2.5 mg or larger produced phase shifts that were significantly different from those produced by the vehicle controls. In addition, the phase-shifting effects of midazolam were completely blocked by administration of the benzodiazepine receptor antagonist, RO 15-1788, indicating that the phase-shifting actions of midazolam are mediated via benzodiazepine receptors. These results indicate that the previously reported effects of triazolam on the circadian clock can be generalized to other short-acting benzodiazepines.

Animals↗
PubMed1989

Administering triazolam on a circadian basis entrains the activity rhythm of hamsters.

A single injection of the short-acting benzodiazepine, triazolam, can induce permanent phase shifts in the circadian rhythm of locomotor activity in free-running hamsters, with the direction and magnitude of the phase shifts being dependent on the circadian time of treatment. The shape of the "phase-response curve" to triazolam injections is totally different from that for light pulses. These findings raise the possibility that repeated injections of triazolam on a circadian basis might be capable of entraining the circadian pacemaker underlying the activity rhythm of hamsters and that the entrainment pattern might differ from that observed in animals entrained to light pulses. To test this hypothesis, blind hamsters received intraperitoneal injections of triazolam (or vehicle) every 23.34, 23.72, 24.00 or 24.66 h for 19-20 days, and the effect of these injections on the period of the rhythm of wheel-running behavior was determined during and after treatment. Repeated injections of 0.1 mg triazolam at these time intervals resulted in the entrainment of the activity rhythm in 36 of 40 animals, whereas 0 of 40 animals entrained to vehicle injections. Importantly, the phase relationship between triazolam injections and the circadian activity rhythm was dependent on the period of drug treatment and could be predicted from the phase-response curve to single injections of triazolam. These phase relationships are dramatically different from those observed between the activity rhythm and 1-h light pulses presented at similar circadian intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

SCN lesions abolish ultradian and circadian components of activity rhythms in LEW/Ztm rats.

A trimodal locomotor activity pattern has been observed in LEW/Ztm rats. Complete and partial lesions of the suprachiasmatic nucleus (SCN) were used to determine whether the same neural substrate may underlie the circadian rhythms and the ultradian modulation of wheel-running activity in these rats. Whereas sham lesions had little or no effect on the wheel-running activity pattern, complete SCN lesions resulted in a complete loss of circadian and ultradian activity components under free-running or 12:12 h light-dark cycle (12:12 LD) conditions. Ultradian and circadian activity components were still present after partial SCN lesions. Periodogram analysis for any given animal revealed that the ultradian periods were always submultiples of the entrained or free-running circadian period. Furthermore there was a high correlation between the amplitudes of circadian and ultradian spectral estimates, but with a different slope in males and females. These results indicate that in LEW/Ztm rats the SCN contributes to the control of both the circadian wheel-running rhythm and the trimodal ultradian modulation of that behavior.

Activity Cycles↗
PubMed1989

Use of benzodiazepines to manipulate the circadian clock regulating behavioral and endocrine rhythms.

Extensive studies have now been carried out demonstrating that the systemic administration of the short-acting benzodiazepine, triazolam, can have pronounced effects on both behavioral and endocrine circadian rhythms. For example, three daily injections of triazolam can phase-advance the circadian rhythm of pituitary luteinizing hormone release and locomotor activity by about 2-3 h in female hamsters maintained in constant light. Triazolam has also been found to facilitate the rate of reentrainment of the activity rhythm following an 8-hour advance or delay in the light-dark cycle. Limited studies with other short-acting benzodiazepines indicate that the effects of triazolam on the circadian system of hamsters can be generalized to this class of drugs. Recent studies in humans indicate that treatment with triazolam can alter the time it takes for human endocrine rhythms to become reentrained following an 8-hour delay in the sleep-wake and light-dark cycle. Such findings raise the possibility that short-acting benzodiazepines may prove useful in reducing the symptoms associated with 'jet-lag' and rotating shift-work schedules as well as in the treatment of various physical and mental illnesses that have been associated with a disorder of biological timekeeping.

Animals↗