Twenty-Four Hour Rhythms of Norepinephrine and Serotonin in Nucleus Suprachiasmaticus, Raphe Nuclei, and Locus Coeruleus in the Rat

Abstract

Summary: Twenty-four hour rhythms, at 4 h intervals, of norepinephrine (NE) and serotonin (5-HT) contents were investigated in the rat brain regions where sleep-wakefulness regulation is believed to occur: Nucleus suprachiasmaticus (SC), n, raphe dorsalis (RD) and medialis (RM), and locus coeruleus, Cosinor method of Halberg was applied to evaluate sinusoidal rhythmicity of the measured values, In the SC only NE showed a significant rhythm with a peak value at the beginning of the light period, which suggests that a NE mechanism may be involved in oscillating biological rhythms in rats, In the RD and RM, 5-HT and 5-hydroxyindoleacetic acid increased significantly during the light period, Moreover, 5-HT rhythm in the RD was maintained even under constant dark conditions, which suggests that 5-HT rhythm in the RD may be endogenous, Key Words: Twentyfour hour rhythm-Norepinephrine-Serotonin-Nucleus suprachiasmaticusRaphe nuclei-Locus coeruleus, Most physiological functions in rodents, such as locomotion, feeding and drinking, thermoregulation, and hormonal secretion, exhibit circadian rhythms. These rhythms are believed to be controlled by a pacemaker located in the nucleus suprachiasmaticus (SC) of the hypothalamus (1). Physiological rhythms may be affected by biochemical changes in the brain. It has been demonstrated that norepinephrine (NE) and serotonin (5-HT) contents in the whole brain or some brain regions change over a 24 h period (2-6). Recently Ibuka et al. (7) found that the sleep-wakefulness cycle is also regulated by the circadian pacemaker in the SC. Although Jouvet has recently modified his monoamine hypothesis of sleep and stressed the importance of the cholinergic mechanisms (8,9), studying the interactions between 5-HT and NE in sleep-wakefulness regulation is still useful.We have studied the 24 h changes in 5-HT and NE contents in the n. raphe dorsalis (RD) and medialis (RM), locus coeruleus (LC), and SC in the rat. To investigate whether a 24 h rhythm in the raphe nuclei is endogenous, an additional experiment was carried out.

Hippocampal Noradrenaline and Serotonin Release over 24 Hours as Measured by the Dialysis Technique in Freely Moving Rats: Correlation to Behavioural Activity State, Effect of Handling and Tail‐Pinch

“…Various authors have previously reported a diurnal rhythm of NA, S H T , and 5-HIAA tissue levels in the brain stem, as well as in several terminal areas of the monoaminergic projections. In the rat, higher levels of NA (Semba et al, 1984;&yen et al, 1986) Handling and t a i l pinch and 5-HT (Quay, 1968;Htry et al, 1972Htry et al, , 1977Semba et al, 1984;&yen et al, 1986) were detected during the light period of the 24 h cycle, whereas 5-HIAA levels were higher during the dark period (Schwartz and Aghajanian, 1969;HCry et al, 1977). These findings have generally been interpreted as an enhanced transmitter utilization during the night, although it has not been possible to exclude the possibility that the variations could have reflected an increased transmitter synthesis during the light period (HCry et al, 1972).…”

“…The noradrenaline (NA) and 5-hydroxytryptamine (5-HT) systems have been implicated in the regulation of sleep and vigilance states (see, e.g., Quay, 1968;Jouvet, 1972;McGinty and Harper, 1976;HCry et al, 1977;Trulson and Jacobs, 1979;Rasmussen et al, 1984;Semba et al, 1984;Aston-Jones, 1985;Shima ef al., 1986;Agren er ul., 1986;for review, see Foote et al, 1983). The extracellular levels of these transmitters in awake animals can, therefore, be expected to vary substantially over time.…”

Noradrenaline Induces Clock Gene Per1 mRNA Expression in C6 Glioma Cells Through β2-Adrenergic Receptor Coupled With Protein Kinase A – cAMP Response Element Binding Protein (PKA–CREB) and Src-Tyrosine Kinase – Glycogen Synthase Kinase-3β (Src–GSK-3β)

“…Noradrenergic fibers and terminals also are present in the SCN (13). Semba et al (14) demonstrated that NA levels in rat SCN are high during periods of light and low during periods of darkness, pointing to circadian oscillation of NA levels. Moreover, NA might modulate SCN circadian rhythms by regulating expression of arginine-vasopressin and vasoactive intestinal peptides, substances hypothesized to participate in control of circadian rhythms (15).…”

Circadian rhythm in the function of central 5-HT1A receptors is endogenous in nature

“…Based on the findings that daily fluctuations of 5-HT levels are found in the hypothalamus and olfactory bulbs of the hamster under LD conditions, but not under continuous light and DD conditions, Ferraro and Steger [8] concluded that daily fluctuations in brain 5-HT levels are driven by the photic cycle and are not circadian in nature. In contrast, other studies found that the rhythms of 5-HT levels in rat raphe nuclei are regulated by an endogenous oscillator [7,9] and by light [7]; this was based on the evidence that the rhythms are maintained under DD conditions, that the 5-HT peak detected on day 3 in DD conditions is about 12 h out of phase with the peak found under LD conditions, and that there is a significant increase in 5-HT levels soon after animals are re-exposed to continuous light [7]. In the present study, the rhythm in the 8-OH-DPAT-induced behavioural response persisted in DD conditions; the pattern of the rhythm observed under DD conditions was similar to that observed under LD conditions, except for the phase change that corresponded to the period of the free-running rhythm.…”

“…The exception is the rhythm in 5-HT levels, which has been investigated in three studies [7 -9]. Disregarding regional differences in the brain, the authors came to three different conclusions: an endogenous rhythm [9], an exogenous rhythm [8], and an endogenous rhythm that is influenced by light [7]. It has been suggested that the functions of the central 5-HT-ergic system, based on central 5-HT 1A [10] and 5-HT 2A receptors [11 -13], exhibit circadian rhythms.…”