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C F Ehret

Publications and source records attributed to C F Ehret.

At least 19 recordsLinked to original sources

Circadian manifestations of barbiturate habituation, addiction and withdrawal in the rat.

The thermal acrophase for the circadian oscillation of core temperature in Charles River male rats fed ad libitum and entrained by light (12 hr dim light and 12 hr bright light) (DL 12:12 hr) occurred near the middle of the dim phase on a control diet of 30% protein. Dietary phenobarbital (0.25%) caused an increase in amplitude of the oscillation (from 0.7 degrees to 1.2 degrees C) and a phase-angle difference (psi-advance) between the zeitgeber and the biological oscillation of about 32 degrees, equivalent to an advance in the thermal acrophase of 2.1 hr in the steady-state. Food consumption was monitored continually and was nearly the same in the two groups; however, animals on the control diet ate around the clock, albeit at a greater rate during dim light than during the bright light phase, whereas rats on phenobarbital started to eat earlier and confined their feeding almost exclusively to early dim phase. This pattern of increase in amplitude of the thermal oscillation and of feeding closely resembling programmed feeding, persisted in phenobarbital-treated animals even in the absence of a dim light-bright light (DL) zeitgeber for eight days. Similar behavior was seen in rats entrained by illumination cycles of 17 hr of dim light and 7 hr of bright light, but with this reduced phase ratio for the zeitgeber, few psi-shifts occurred, and these were smaller than those induced in the group receiving 12 hr of dim light and 12 hr of bright light. In each group, introduction of the drug into the diet and, even more noticeably, removal of the drug from the diet, induced transients of circadian dyschronism that persisted for 4-5 days.

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Relationship between field strength and arousal response in mice exposed to 60-Hz electric fields.

White-footed mice, Peromyscus leucopus, were exposed to 60-Hz electric fields to study the relationship between field strength and three measures of the transient arousal response previously reported to occur with exposures at 100 kV/m. Five groups of 12 mice each were given a series of four 1-h exposures, separated by an hour, with each group exposed at one of the following field strengths: 75, 50, 35, 25, and 10 kV/m; 8 additional mice were sham-exposed with no voltage applied to the field generator. All mice were experimentally naive before the start of the experiment, and all exposures occurred during the inactive (lights-on) phase of the circadian cycle. The first exposure produced immediate increases in arousal measures, but subsequent exposures had no significant effect on any measure. These arousal responses were defined by significant increases of gross motor activity, carbon dioxide production, and oxygen consumption, and were frequently recorded with field strengths of 50 kV/m or higher. Significant arousal responses rarely occurred with exposures at lower field strengths. Responses of mice exposed at 75 and 50 kV/m were similar to previously described transient arousal responses in mice exposed to 100-kV/m electric fields. Less than half of the mice in each of the field strength groups below 50 kV/m showed arousal responses based on Z (standard) scores, but the arousals of the mice that did respond were similar to those of mice exposed at higher field strengths. Polynomial regression was used to calculate the field strength producing the greatest increases for each of the arousal measures. The results show that the amplitude of the transient arousal response is related to the strength of the electric field, but different measures of arousal may have different relationships to field strength.

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Tissue distribution of cadmium and metallothionein as a function of time of day and dosage.

Cadmium-109 chloride (1 mg or 48 ng Cd2+/kg body wt) was administered intraperitoneally to rats at one of eight selected times of day. Exactly 48 hr later each animal was sacrificed, and the cadmium content of the blood, brain, heart, kidney, liver, and testes was determined. Metallothionein levels in the liver and kidney were also measured. Distribution and retention of cadmium was very different at the different dose levels. Approximately 60% of the higher dose of cadmium was retained in the six tissues examined, while only 11.5% of the lower dose could be accounted for in these six tissues. The liver retained the largest percentage of the administered cadmium at both dose levels, but the magnitude of the retention differed by a factor of 6 (57.3% of the higher dose and 9.6% of the lower dose). The pattern of cadmium distribution among the other tissues was also different. At the 1-mg Cd2+/kg body wt level, the kidneys accumulated the second largest fraction of cadmium, followed by the blood, heart, testes, and brain. In the 48-ng Cd2+/kg body wt groups the order was kidney, testes, blood, heart, and brain. Only in the testes of animals receiving the low dose of cadmium was there an effect of time of day, and here the effect was marked. When cadmium was administered during the dark phase of the daily cycle, the testes contained an average of six times more cadmium than when cadmium was given during the light phase. Similarly, levels of metallothionein in the kidney were significantly higher when cadmium was administered during the dark phase. A trend toward higher metallothionein levels in the liver during the dark phase was also observed, but this trend was not statistically significant.

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Alpha-methyl-p-tyrosine shifts circadian temperature rhythms.

alpha-Methyl-p-tyrosine shifts the acrophase (time of highest temperature) of the circadian temperature rhythm of the rat to earlier or later times of day depending on the phase of the circadian cycle at which the drug is administered. When alpha-methyl-p-tyrosine methyl ester HCl is injected intraperitoneally at a dose of 100 mg/kg late in the projected 8-h light phase, the acrophase of the intraperitoneal temperature rhythm is delayed by up to 3 h. However, when the same dose of drug is given 9-10 h into the projected 16-h dark phase of the daily cycle, the acrophase of the temperature rhythm occurs about 2 h earlier than expected. The times of alpha-methyl-p-tyrosine administration leading to maximal phase delays or advances are correlated with the times of minimal and maximal turnover of norepinephrine in the hypothalamus. These results suggest that changing rates of norepinephrine turnover in the hypothalamus may regulate the circadian temperature rhythm in rats. The results also emphasize the fact that the effects of drugs may vary as a function of the time of administration. This fact must be taken into account in pharmacologic testing.

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Glucocorticosteroid injection is a circadian zeitgeber in the laboratory rat.

Intraperitoneal temperatures were monitored by radiotelemetry to observe the thermoregulatory rhythm of male laboratory rats (Rattus norvegicus albinus) Rats received single injections of dexamethasone (as dexamethasone sodium phosphate) during constant darkness (0.1 lx) with food freely available or no food available. No phase shifts occurred following saline injection or dexamethasone at 1 mg/kg body wt. Depending on the phase of injection relative to the circadian cycle, dexamethasone at 10 mg/kg caused thermoregulatory peaks to be either delayed or advanced on the 4th and 5th day after injection. There was an insensitive interval which corresponded to subjective day. Phase shifts induced by dexamethasone during ad libitum feeding were of less magnitude than those induced during starvation. The determination of phase-shifting parameters (i.e., a phase-response curve) for hormonal substances represents a rigorous and broadly applicable technique for determining endogenous mechanisms for circadian phase control and entrainment.

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Circadian variations in the activity of tyrosine hydroxylase, tyrosine aminotransferase, and tryptophan hydroxylase: relationship to catecholamine metabolism.

Circadian variations in the activity of tyrosine hydroxylase, tyrosine aminotransferase, and tryptophan hydroxylase were observed in the rat brain stem. Tyrosine hydroxylase exhibited a bimodal pattern with peaks occurring during both the light and dark phases of the circadian cycle. Tyrosine aminotransferase had one daily peak of activity occurring late in the light phase, whereas tryptophan hydroxylase activity was maximal late in the dark phase. Circadian fluctuations in tyrosine hydroxylase activity did not correlate well with circadian variations in the turnover rates of norepinephrine or dopamine nor with levels of these catecholamines. This supports the idea that although tyrosine hydroxylase is the rate-limiting enzyme in the synthesis of catecholamines, other factors must also be involved in the in vivo regulation of this process. Administration of alpha-methyl-p-tyrosine (AMT) methyl ester HCl (100 mg/kg) had no effect on the activity of tryptophan hydroxylase, but effectively eliminated the peak of tyrosine hydroxylase activity that occurred during the light phase. AMT also lowered levels of tyrosine aminotransferase, but only at times near the daily light to dark transition. These chronotypic effects of AMT emphasize the importance of "time of day" as a factor that must be taken into account in evaluating the biochemical as well as the pharmacological and toxicological effects of drugs.

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Chronotypic action of theophylline and of pentobarbital as circadian zeitgebers in the rat.

In the rat the deep body temperature rhythm, monitored by telemetry, can be reset in a predictable direction by a stimulant (theopylline) and by a depressant (pentobarbital). When the drugs are applied immediately before or during the early active phases of the circadian cycle, the rhythm is set back (phase delay). When applied later, past the thermal peak, theophylline, but not pentobarbital, shifts the rhythm ahead (phase advance). Theophylline and pentobarbital in addition to having a number of already established pharmacological properties are now further identified as chronobiotics: they are drugs that may be used to alter the biological time structure by rephasing a circadian rhythm.

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