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

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.