In vivo evidence that 5-hydroxytryptamine (5-HT) neuronal firing and release are not necessarily correlated with 5-HT metabolism

Crespi, Francesco; Garratt, Jeni C.; Sleight, Andrew J.; Marsden, C.A.

doi:10.1016/0306-4522(90)90128-q

Cited by 89 publications

(28 citation statements)

References 27 publications

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“…Alternatively, voltammetric studies in other regions of the brain have measured extracellular 5-HIAA, which can potentially be used as an indicator of 5-HT's release, reuptake and then subsequent metabolism (Clement et al, 1998;Crespi et al, 1990;Houdouin et al, 1991). In the IC, however, we found that changes in the combined 5-HIAA+5-HT signal were not correlated with changes in the 5-HT signal during the recovery from anesthesia (Fig.3).…”

Section: Measuring 5-ht With Voltammetrymentioning

confidence: 75%

“…Voltammetry has been used in other regions of the brain to measure 5-HT or the 5-HT metabolite, 5-hydroxy-indole-acetic acid (5-HIAA), as indicators of 5-HT release (Bunin and Wightman, 1998;Crespi et al, 1990;Houdouin et al, 1991) and metabolism (Crespi, 1990;Lindefors et al, 1997). IC 5-HT was measured in conditions that have evoked either increases in the activity of dorsal raphe neurons or increases in 5-HT or 5-HIAA in previous studies, including during the presentation of simple sensory stimuli or stressors.…”

Section: Introductionmentioning

confidence: 99%

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Serotonin in the inferior colliculus fluctuates with behavioral state and environmental stimuli

Hall

Rebec

Hurley

2010

Journal of Experimental Biology

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SUMMARYNeuromodulation by serotonin (5-HT) could link behavioral state and environmental events with sensory processing. Within the auditory system, the presence of 5-HT alters the activity of neurons in the inferior colliculus (IC), but the conditions that influence 5-HT neurotransmission in this region of the brain are unknown. We used in vivo voltammetry to measure extracellular 5-HT in the IC of behaving mice to address this issue. Extracellular 5-HT increased with the recovery from anesthesia, suggesting that the neuromodulation of auditory processing is correlated with the level of behavioral arousal. Awake mice were further exposed to auditory (broadband noise), visual (light) or olfactory (2,5-dihydro-2,4,5-trimethylthiazoline, TMT) stimuli, presented with food or confined in a small arena. Only the auditory stimulus or restricted movement increased the concentration of extracellular 5-HT in the IC. Changes occurred within minutes of stimulus onset, with the auditory stimulus increasing extracellular 5-HT by an average of 5% and restricted movement increasing it by an average of 14%. These findings suggest that the neuromodulation of auditory processing by 5-HT is a dynamic process that is dependent on internal state and behavioral conditions.

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Section: Measuring 5-ht With Voltammetrymentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Serotonin in the inferior colliculus fluctuates with behavioral state and environmental stimuli

Hall

Rebec

Hurley

2010

Journal of Experimental Biology

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“…Parallel effects on DRN discharge and 5-HT terminal release has also been shown for other compounds such as the 5-HT 1A agonist 8-OH-DPAT, which decreases both DRN discharge and terminal 5-HT release (Crespi et al 1990), 5-HT 2 agonists (Wright et al 1990), and serotonin-selective reuptake inhibitors (Romero et al 1996). Furthermore, parallel effects of CRF on LC discharge and terminal norepinephrine release have been demonstrated (Page and Abercrombie 1999;Curtis et al 1997;Smagin et al 1995).…”

Section: Discussionmentioning

confidence: 85%

Effects of Corticotropin-Releasing Factor on Neuronal Activity in the Serotonergic Dorsal Raphe Nucleus

Kirby

Rice

Valentino

2000

Neuropsychopharmacology

278

284

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The present study examined the regional localization of corticotropin-releasing factor (CRF)-and 5-hydroxytryptamine (5-HT)-immunoreactive (IR) fibers within the rat dorsal raphe nucleus (DRN) using immunohistochemistry. Additionally, the effects of CRF, administered intracerebroventricularly (0.1-3.0 g) or intraraphe (0.3-30 ng), on discharge rates of putative 5-HT DRN neurons Corticotropin-releasing factor (CRF) has a diverse range of physiological and behavioral effects, acting both as a neurohormone at the level of the anterior pituitary and as a neurotransmitter in brain. As a neurohormone, CRF initiates the release of adrenocorticotropic hormone which triggers the endocrine limb of the stress response . Anatomical evidence of a widespread distribution of CRF-immunoreactive (IR) terminals and receptors throughout the brain De Souza et al. 1985;Potter et al. 1994;Sakanaka et al. 1987;Swanson et al. 1983) provides support for the additional role of CRF as a brain neurotransmitter. An example of a potential neurotransmitter action of CRF is its action on the locus coeruleus (LC)-norepinephrine system. Intracerebroventricular (i.c.v.) or intracoerulear administration of CRF increases activity of LC neurons Page and Abercrombie 1999;Valentino et al. 1983) and stimulates NE release in terminal fields of the LC (Lavicky and Dunn 1993;Page and Abercrombie 1999;Smagin et al. 1995). Moreover, activation of LC neurons by certain physiological stimuli is attenuated by CRF antagonists administered into the LC (Curtis et al. 1994;Lechner et al. 1997).Anatomical evidence suggests that CRF is also positioned to affect activity of the dorsal raphe nucleus Philadelphia, PA 19102. Received May 17, 1999; revised July 28, 1999; accepted August 3, 1999. N EUROPSYCHOPHARMACOLOGY 2000 -VOL . 22 , NO . 2 CRF Effects on 5-HT Neurons 149 (DRN)-5-hydroxytryptamine (5-HT) system. Thus, CRF receptor binding sites (De Souza et al. 1985) and mRNA Potter et al. 1994) as well as CRF-IR terminals (Sakanaka et al. 1987;Swanson et al. 1983) are localized in the DRN, a primary site of 5-HT cell bodies projecting to the forebrain. Recent studies demonstrated that relatively low doses of CRF (administered i.c.v.) inhibit 5-HT release in two different terminal regions of the DRN (i.e., striatum and lateral septum), suggesting that the site of action of CRF effects on 5-HT release is at the level of the cell bodies in the DRN . Consistent with this, electrophysiological recordings indicated that a low dose of CRF (administered i.c.v.) that decreased extracellular levels of 5-HT in striatum also decreased DRN discharge rate . In contrast to the effects of low doses of CRF, higher doses were found to not alter or to increase extracellular 5-HT levels in the lateral septum or striatum, respectively. The complex dose-related effects of CRF on 5-HT release could be a function of multiple CRF receptor subtypes within the DRN and/or different sites of action (cell bodies vs. terminals) of i.c.v. administered CRF.The present study was designed t...

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“…At present, the significance of extracellular levels of 5-HIAA is not yet fully resolved. Evidence has been accumulating showing that 5-HIAA levels in dialysates do not reflect the metabolism of 5-HT previously being released (Auerbach et al, 1989;Crespi et al, 1990;Wright et al, 1992;Linthorst et al, 1994, Rueter et al, 1997. Instead, extracellular 5-HIAA seems to be largely derived from metabolism of the spillover of newly synthesized, yet unreleased 5-HT, and hence may be regarded as an index for the level of synthesis of 5-HT within serotonergic neurons (see Grahame-Smith, 1974;Kuhn et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

Altered Serotonergic Neurotransmission but Normal Hypothalamic–Pituitary–Adrenocortical Axis Activity in Mice Chronically Treated with the Corticotropin-Releasing Hormone Receptor Type 1 Antagonist NBI 30775

Oshima

Flachskamm

Reul

et al. 2003

Neuropsychopharmacol

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Antagonists of the corticotropin-releasing hormone receptor type 1 (CRH-R1) are regarded as promising tools for the treatment of stress-related psychiatric disorders. Owing to the intricate relationship between CRH and serotonin (5-HT), we studied the effects of chronic oral treatment of C57Bl6/N mice with the CRH-R1 antagonist NBI 30775 (formerly known as R121919) on hippocampal serotonergic neurotransmission during basal (on 15th day of treatment) and stress (forced swimming; on 16th day of treatment) conditions by in vivo microdialysis. Given the important role of CRH in the regulation of hypothalamic-pituitary-adrenocortical (HPA) axis activity and behavior, the effects of NBI 30775 on dialysate-free corticosterone levels, and on home cage and forced swimmingrelated behavior were also assessed. Chronic administration of NBI 30775 (18.4 7 0.9 mg/kg/day) did not result in alterations in food consumption and body weight. NBI 30775 caused complex changes in hippocampal serotonergic neurotransmission. Whereas no effects on the diurnal rhythms of 5-HT and its metabolite 5-hydroxyindoleacetic acid were found, the responses of the neurotransmitter and its metabolite to 10 min of forced swim stress were reduced and prolonged, respectively. NBI 30775 did not change free corticosterone levels over the diurnal rhythm. Moreover, NBI 30775-treated mice showed a similar forced swim stress-induced increase in corticosterone as observed in the control group. No effects of NBI 30775 on home cage, and swim stress-related active behaviors (climbing, swimming) and immobility were found. Thus, whereas chronic antagonism of CRH-R1 did not compromise HPA axis performance and behavior, distinct changes in serotonergic neurotransmission developed. Owing to the important role of 5-HT in the pathophysiology of mood and anxiety disorders, the latter observation may contribute to the therapeutical efficacy of CRH-R1 antagonists in these illnesses.

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In vivo evidence that 5-hydroxytryptamine (5-HT) neuronal firing and release are not necessarily correlated with 5-HT metabolism

Cited by 89 publications

References 27 publications

Serotonin in the inferior colliculus fluctuates with behavioral state and environmental stimuli

Serotonin in the inferior colliculus fluctuates with behavioral state and environmental stimuli

Effects of Corticotropin-Releasing Factor on Neuronal Activity in the Serotonergic Dorsal Raphe Nucleus

Altered Serotonergic Neurotransmission but Normal Hypothalamic–Pituitary–Adrenocortical Axis Activity in Mice Chronically Treated with the Corticotropin-Releasing Hormone Receptor Type 1 Antagonist NBI 30775

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