The Nature and Magnitude of in vivo 5-Hydroxyindoleacetic Acid Output from 5-Hydroxytryptamine Terminals Is Related to Specific Regions of the Suprachiasmatic Nucleus

Abstract

Eight cycling female rats were implanted with push-pull cannulae over the region of the suprachiasmatic nuclei (SCN) and allowed 7–10 days for recovery. Perfusion of the SCN continued in these freely behaving rats for 5–6 h of the light period and the subjective scotophase. The release of 5-hydroxyindoleacetic acid (5-HIAA) ranged from 10 to 350 pg 5-HIAA/min. Significantly, the amplitude and characteristics of the output of 5-HIAA were highly location dependent in that rostral cannulae placements revealed high amplitude changes with initial mean values of 40 pg 5-HIAA/min, which increased toward the dark phase to mean peak values of 195 pg 5-HIAA/min. Caudal cannulae placements revealed a low amplitude, high frequency, basal type of 5-HIAA release which did not increase toward the dark period (approximately 5 pg/min). 5-Hydroxytryptophan infusion resulted in a significant marked increase in the basal release of 5-HIAA confirming the biochemical viability of the area undergoing perfusion. These results suggest that the in vivo measurement of 5-HIAA from 5-hydroxytryptamine (5-HT) terminals in the region of the SCN could reflect discrete functional activity of serotonergic terminals within specific regions of the SCN in a freely behaving rat. Furthermore, the biochemical viability of these 5-HT terminals and the ability of the rat’s SCN to exhibit marked differential changes in 5-HT activity emphasizes the physiological relevance of this model system to study neuroendocrine events in freely behaving animals.

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

“…Our results are consistent with those of previous studies using in vivo voltametric [26] and push-pull cannula [27] methodologies in the rat SCN, in which marked daily variation in 5-HIAA release was observed. In each study, extracellular 5-HIAA release rose during late subjective evening and peaked near the time of lights-ofT.…”

“…In conclusion, the daily pattern of 5-HIAA release in the male Siberian hamster SCN is comparable to that measured in the rat using push-pull cannulation [27] or voltametiy [26]. The increased inhibitory effect of TTX on 5-HIAA release during the dark phase, compared to the light phase, is evidence that there is a nocturnal increase in serotonergic transmission within the SCN.…”

“…Although the basis for the action ofserotonin in the SCN has not yet been established, diurnal rhythms in hypothalamic serotonin concentration [25,38,39], uptake [23,24] and electrophysiological effects [4,21,40] have been observed. Moreover, striking diurnal fluctuations in the extracellular concentra tion of the principal serotonin metabolite, 5-HIAA, have been documented in the mammalian SCN [26,27], Collec tively, these results give strong evidence that modulation of responsiveness of serotonin targets in the SCN together Time, min with regulated timing of serotonin release are important to the regulation of pacemakerfunction.…”

“…A daily rhythm in release of serotonin may be involved in this process, since in vivo techniques including voltammetry [26], and push-pull cannulation [27] have revealed a striking daily variation in the extracellular concentration of the principal serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in the SCN. The significance of the 5-HIAA rhythm is not certain, however, because there is a large body of evidence suggesting that extrac ellular 5-HIAA may be derived primarily from intracel lular metabolism of unreleased serotonin [4,[28][29][30][31][32][33].…”

Bromocriptine Reduces Obesity, Glucose Intolerance and Extracellular Monoamine Metabolite Levels in the Ventromedial Hypothalamus of Syrian Hamsters

“…It is likely that these neurotransmitters are undetectable in the synaptic space of hamsters [19] due to rapid turnover unless the reuptake mechanism is blocked [20]. Although there is uncertainty about functional relationships of metabolites to synaptic neurotransmitter activity, largely due to the limitations in the current in vivo methodology for resolving the release of extracellular neurotransmitters [21] as well as based on results from acute pharmacological studies [22, 23], many investigators have established the principle that the measurement of monoamine metabolite levels in the extraneuronal spaces of the brain is a valid index of neurotransmitter activity in vivo [24, 25, 26], especially under steady-state conditions (as in the present study).…”