Diurnal Variation in 5-Hydroxyindole-Acetic Acid Output in the Suprachiasmatic Region of the Siberian Hamster Assessed by in vivo Microdialysis: Evidence for Nocturnal Activation of Serotonin Release

Abstract

In vivo brain microdialysis was used to characterize the daily pattern of 5-hydroxyindole-acetic acid (5-HIAA) release in the region of the suprachiasmatic nuclei (SCN) in freely behaving male Siberian hamsters housed under 16L:8D. A marked diurnal variation in the concentration of extracellular 5-HIAA was apparent, with peak levels (147 ± 5% of the daily mean; p < 0.05) occurring 2-3 h after lights-off. Smaller nocturnal rises in extracellular 5-HIAA were observed in the posterior hypothalamus and preoptic area (128 ± 4 and 123 ± 8% of the daily mean, respectively; both p < 0.05 vs. average daytime levels). Tryptophan loading increased 5-HIAA in SCN microdialysates by 44 ± 6%, and this response was enhanced by localized perfusion with tetrodotoxin (TTX; 5 µM). Localized applications of KC1 (150 mil) or veratridine (100 µM) decreased 5-HIAA by 62 ± 5 or 49 ± 11%, respectively. The effect of KC1 was not significantly affected by specific calcium channel blockers. Perfusion with TTX markedly decreased SCN 5-HIAA during the dark phase, but had little effect during the light phase (42 ± 8 vs. 12 ± 5% suppression, respectively; p < 0.01). Addition of serotonin (3 µM) to the perfusate significantly stimulated 5-HIAA output. This treatment increased the release of 5-HIAA more during the dark than during the light phase (61 ± 8 vs. 25 ± 5%, respectively; p < 0.01). Taken together, these results are evidence that: (1) there is increased TTX-sensitive (synaptic) release of serotonin at night that could contribute to the nocturnal rise in the extracellular concentration of 5-HIAA in the SCN; (2) clearance (uptake and/or metabolism) of extracellular serotonin in the SCN is higher at night; (3) 5-HIAA release in the SCN of the Siberian hamster is similar to that reported for other areas of the brain in other species, and (4) variations in 5-HIAA may, under certain physiological conditions, reflect changes in the extracellular concentration of serotonin.

Both Neuropeptide Y and Serotonin Are Necessary for Entrainment of Circadian Rhythms in Mice by Daily Treadmill Running Schedules

“…Recent studies further indicate that photic entrainment is likely mediated by glutamatergic retinal afferents to the SCN (Ebling, 1996) and that both 5-HT and NPY provide inhibitory modulation of this input (Biello, 1995;Weber et al, 1995;Miller et al, 1996; but see Shibata et al, 1994) (glutamate may in turn inhibit N PY, Biello et al, 1997). Both 5-HT and N PY activity within the SCN are increased during periods of behavioral arousal and activity (Jhanwar-Uniyal et al, 1991;Glass et al, 1992;Shinohara et al, 1993;Dudley and Glass, 1996) and may mediate inhibition of photic shifting by concurrent behavioral activity (Ralph and Mrosovsky, 1992). Behavioral activity also can phase shift and entrain circadian rhythms, independent of retinal input to the pacemaker.…”

In VivoResetting of the Hamster Circadian Clock by 5-HT7Receptors in the Suprachiasmatic Nucleus

“…Starting at 1 d after the last p-C PA or vehicle injection, 3 hr SC N perf usions began at Z T 6 in animals receiving the 5-HT 1A,7 receptor agonist 2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydro-naphthalene (8-OH-DPAT) (Sigma) or 5-HT creatinine sulfate (Sigma) in 94.5:5.5% AC SF/ DMSO v/ v [the perf usate free-base concentration of each agonist was 1.2 mM; with an ϳ2.4% in vitro probe efficiency for indoleamines (Glass et al, 1992), the external concentrations of both agonists was estimated at ϳ30 M]. Control animals received AC SF/ DMSO vehicle.…”

Glucocorticoids up-regulate the expression of glial fibrillary acidic protein in the rat suprachiasmatic nucleus

“…This is of particular interest because it allows the assumption that corticosterone/5-HT interactions in the raphe nuclei may play important roles in synaptic reorganizations that might occur in the SCN over the 24-h cycle. Highly relevant in this context are experimental data showing daily variations in indices of serotoninergic activity in the SCN (Cagampang and Inouye, 1994;Faradji et al, 1983;Glass et al, 1992;Ramirez et al, 1987) and a more recent report of an endogenous rhythm in 5-HT release that could be importantly determined by the circadian activity rhythm (Dudley et al, 1998). Assuming that fluctuations of GFAP levels in the SCN do result from interactions of corticosterone with midbrain raphe 5-HT neurons, then the rhythmic pattern of intra-SCN 5-HT release might be entrained by the circadian fluctuations of corticosterone.…”