Lack of circadian rhythm in plasma levels of 3,4-dihydroxyphenylethyleneglycol in healthy human subjects

In order to investigate the possible existence of a circadian rhythm in plasma free and sulfate-conjugated 3,4-dihydroxyphenylethyleneglycol (DOPEG), the plasma levels of this metabolite (and for comparison, of melatonin and cortisol) were measured in seven healthy volunteers at 4-h intervals over a period of 24 h. Plasma concentrations of melatonin and cortisol showed distinct diurnal variations with acrophases at 2.5 h and 8.5 h, respectively. In contrast, plasma free DOPEG levels were relatively stable over the 24-h period studied. Sulfate-conjugated and free + sulfate-conjugated DOPEG levels showed a slight, non-significant increase in the early afternoon. These results indicate that in contrast to plasma 3-methoxy 4-hydroxyphenylethyleneglycol, plasma free and conjugated DOPEG levels do not exhibit a circadian rhythm.     

Discrimination of circadian phase in intact and suprachiasmatic nuclei-ablated rats

This study examined whether the circadian system of rats can serve as a consulted clock for discriminating time of day. Food restricted rats housed in activity wheels were trained to lever press for food in a two-lever T-maze in which the left arm was correct in a morning feeding session, and the right arm in an afternoon session (7 h interval). All six rats learned the task (discrimination ratios>chance on 85–95% of sessions) and exhibited anticipatory wheel running prior to most sessions. Performance was not disrupted by inverting the LD cycle or by omitting 1–3 sessions, indicating that learning was not dependent on light-dark cues, alternation strategies, or physiological states associated with intermeal interval. Five of six additional rats with ablations of the suprachiasmatic nucleus light-entrainable pacemaker acquired the discrimination, indicating that time-of-day cues can be provided by another circadian pacemaker (likely food-entrainable). The results provide the first clear evidence that the circadian system in a mammal can function as a consulted clock that provides discriminative time cues for cognitive processes subserving behavioral plasticity.     

Cardiovascular rhythm effects of gamma recombinant DNA interferon

Summary Twenty patients receiving recombinant DNA gamma interferon were prospectively assessed for cardiac rhythm disturbances. All patients were evaluated with baseline electrocardiograms, pretreatment ambulatory monitoring and ejection fraction determination. Each patient was then monitored continuously during drug administration. Quantitative ventricular ectopy was not increased, nor were average heart rate, maximal heart rate, or quantitative supraventricular ectopy when comparing baseline to during therapy parameters. Complex cardiac ectopy and noteworthy cardiac events (NCE) were defined and identified in 2/20 (10%) patients pretreatment, and in 8/18 patients (44%) with normal baseline tracings during treatment (p = .02). This difference was not apparent when corrected for total days monitored pre and post treatment (p > .2). These consisted predominantly of nonsustained short duration ventricular tachycardia (seven of eight patients). We conclude that life threatening cardiac events are uncommon with gamma interferon therapy.The opinions or assertions contained herein are the private views of the authors and are not to be construed as reflecing the view of the Department of the Army or the Department of Deferoe.     

The effects of chronic lithium on the EEG and locomotor response to drug challenge in rats

Adult male Wistar rats were given lithium as a dietary supplement or a control diet for a period of eight weeks. Spectral analysis of cortical EEG activity revealed a significant shift in the amplitude and variance of the theta rhythm in rats administered lithium. A significant increase in the locomotor response to morphine over time but not to saline or caffeine was seen in lithium treated rats as compared to controls. The modulation of the locomotor response to morphine seen following lithium administration suggests the possibility that modification of a brain opioid system may contribute to the clinical response to lithium.     

Rats prefer ambient temperatures out of phase with their body temperature circadian rhythm

Rats placed in thermally graded enclosures cyclically selected ambient temperatures about 195 degrees out of phase with the circadian variations of their hypothalamic temperature. This finding cannot be explained by the generally accepted assumption that body temperature circadian rhythm is due to a cyclic shift of the set-point temperature.     

Binding Characteristics, Regional Distribution and Diurnal Variation of [125I]-Iodomelatonin Binding Sites in the Chicken Brain

The [125I]-iodomelatonin binding sites in chicken brain membrane preparations were studied. The binding of [125I]-iodomelatonin to the membrane preparations of chicken brain was rapid, stable, saturable, and reversible. The order of pharmacological affinities of [125I]-iodomelatonin binding sites in the chicken brain membrane preparations was: melatonin greater than 6-chloromelatonin greater than N-acetylserotonin greater than 5-hydroxytryptamine greater than tryptamine greater than 5-methoxytryptophol, much greater than 1-acetylindole-3-carboxaldehyde, 5-hydroxyindole-3-acetic acid, L-tryptophan, 5-hydroxytryptophan, 3-acetylindole. Compounds known to act on the receptor of norepinephrine or acetylcholine were inactive as compared to melatonin. Among the various brain regions studied, melatonin binding had maximal level in the hypothalamus, intermediate levels in the mid-brain, ponsmedulla, and telencephalon, and minimum level in the cerebellum. Subcellular fraction studies indicated that 40% of the binding was located in the mitochondrial fraction, 27% in the nuclear, 26% in the microsomal, and 6% in the cytosol fraction. Scatchard analysis of the membrane preparations revealed a dissociation constant (Kd) of 199.6 +/- 17 pM and a total number of binding sites (Bmax) of 16.6 +/- 0.75 fmol/mg protein at midlight. Thus, our results showed the presence of specific melatonin binding sites in the chicken brain membrane preparations. Saturation studies demonstrated that [125I]-iodomelatonin binding capacity in chicken brain membrane preparations were 40% greater at midlight (16.6 +/- 0.75 fmol/mg protein) than at middark (10.6 +/- 0.56 fmol/mg protein), with no significant variation in their binding affinities.     

Circadian rhythm of rectal temperature in man with two different types of clothing

Summary We compared the circadian rhythm of human rectal temperature with two different types of clothing at an ambient temperature of 27.5° ± 0.5°C and a relative humidity of 40 ± 10%. One clothing covered the whole body area except for the head, hands and feet (Type A, weight 475g, 0.98 clo), the other covered the trunk, upper arms and thighs (Type B, weight 366 g, 0.93 clo). Major findings are summarized as follows: (1) Late evening fall after retiring and a morning rise after rising in the rectal temperature rhythm were significanty quicker in Type B than in Type A. (2) Late evening rise after retiring and a morning fall after rising in the skin temperatures of the extremities were quicker in Type B than in Type A. (3) A range of oscillation in the circadian rectal temperature rhythm was significantly larger in Type B than in Type A. It was suggested that the quicker late evening rise and morning fall of the skin temperatures in the extremities after retiring and rising, respectively, might be responsible for the quicker late evening fall and morning rise of the circadian rectal temperature.     

Strain difference in behavioral response to a new environment in rats

Abstract Locomotor activity in rats throughout a 24-hour period in a new environment was examined for strain differences and for the capacity for adaptation to that environment. Fischer 344 rats (F344), spontaneously hypertensive rats (SHR) and Wistar normotensive Kyoto rats (WKY) were used. The horizontal locomotor activity of individual rats was measured by photocell-utilizing activity-recording devices. The locomotor activity counts on the second day, after 1 day of adaptation, were compared with those after 5 days of adaptation (on the sixth day). In WKY, there was no difference in activity at any period of the day between the second and sixth days. In SHR, the locomotor activity on the second day between 6:00 h and 9:00 h (in the light phase) and between 24:00 h and 3:00 h (in the dark phase) was higher than on the sixth day. In F344, the locomotor activity on the second day between 18:00 h and 2:00 h was higher than on the sixth day. The capacity for adaptation in SHR and F344 was thus poorer than in WKY. The poor adaptation in SHR and F344 was similar to that in depressive patients induced by moving house. These findings suggested that SHR or F344 were suitable for depression research.