The effect of oral 5-HTP administration on 5-HTP and 5-HT immunoreactivity in monoaminergic brain regions of rats

Lynn-Bullock, Christina P.; Welshhans, Kristy; Pallas, Sarah L.; Katz, Paul S.

doi:10.1016/j.jchemneu.2004.02.003

Cited by 57 publications

(43 citation statements)

References 24 publications

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“…Although it is widely assumed that oral administration of 5-HTP results in increased synaptic release of 5-HT from cells in the raphe nuclei (Birdsall, 1998;Turner et al, 2006), empirical evidence to support this view is limited. In rats, relevant oral doses of 5-HTP (given without the coadministration of MAO inhibitors) result in increased 5-HTP and 5-HT immunoreactivity in the dorsal raphe nucleus, suggesting that 5-HTP is effectively transported across the blood-brain barrier and decarboxylated into 5-HT (Lynn-Bullock et al, 2004). Although several animal studies have demonstrated that 5-HTP administration can increase 5-HT levels in the central nervous system (reviewed in Lynn-Bullock et al, 2004), it remains unknown if these increases reflect functionally meaningful synaptic 5-HT release and stimulation of 5-HT activity over the long term (Meyers, 2000), or if enhancements in 5-HT release are unlikely due to regulation by autoreceptors (Suter and Collard, 1983).…”

Section: Introductionmentioning

confidence: 99%

Oral administration of 5‐hydroxytryptophan (5‐HTP) impairs decision making under ambiguity but not under risk: evidence from the Iowa Gambling Task

Gendle

Golding

2010

Human Psychopharmacology

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Section: Introductionmentioning

confidence: 99%

Oral administration of 5‐hydroxytryptophan (5‐HTP) impairs decision making under ambiguity but not under risk: evidence from the Iowa Gambling Task

Gendle

Golding

2010

Human Psychopharmacology

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“…Portions of excreted urine were collected over 4 h. The increase in endogenous brain serotonin was produced by intraperitoneal injection of the rate-limiting precursor of serotonin biosynthesis, 5-HTP (Calbiochem, 5 mg/100 g body weight). We did not measure brain serotonin because it has been amply reported that a single intraperitoneal injection of 5-HTP to rats caused a fast and significant increase in the level of serotonin not only in plasma, but also in the brain because it rapidly passed through the blood brain barrier [22, 36, 37]. …”

Section: Methodsmentioning

confidence: 99%

“…Thus, it has been reported that serotonin may exert an inhibitory or virtually no in vivo or in vitro effect on AVP synthesis and secretion [11, 18, 19]. The experimental results reported for fluoxetine, a serotonin reuptake inhibitor, are also inconsistent [20,21,22]. Meanwhile there is ample evidence indicating that serotonin, its precursor, 5-hydroxytryptophan (5-HTP), and certain serotonin receptor agonists stimulate AVP release into peripheral blood [23,24,25,26,27].…”

Section: Introductionmentioning

confidence: 99%

“…The aim of the current study was to examine the effect of 5-HTP, known to increase endogenous brain serotonin level under intraperitoneal injection [22, 36, 37], on the osmoregulatory response to intragastric water and a 2% NaCl solution load in Wistar rats with normal AVP synthesis compared with homozygous Brattleboro rats congenitally lacking AVP.…”

Section: Introductionmentioning

confidence: 99%

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Effect of an Increase in Brain Serotonin on the Osmoregulatory Response to a Hypo- or Hyperosmotic Load in Wistar and Vasopressin-Deficient Brattleboro Rats

2007

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Serotonin and its receptor agonists stimulate the release of arginine vasopressin (AVP) into peripheral blood under intraventricular injection. To test the hypothesis that brain serotonin can modulate the development of natural osmoregulatory responses, the effect of an increase in endogenous brain serotonin on the response to an intragastric hypo- or hyperosmotic loading was studied in Wistar and AVP-deficient Brattleboro rats. 5-Hydroxytryptophan (5-HTP), the rate-limiting serotonin biosynthesis precursor known to increase the brain level of serotonin, was injected intraperitoneally (5 mg/100 g body weight). The renal functional parameters (glomerular filtration rate [GFR], free water reabsorption, and urine flow rate) were monitored during the 4 h after intragastric infusion of water or a 2% NaCl solution (5% of body weight). Plasma AVP was measured by radioimmunoassay. In Wistar rats, intraperitoneal injection of 5-HTP at the same time as water loading prevented the development of the renal diuretic response: there was no increase in urine flow rate and GFR, and free water reabsorption remained at the high level. In AVP-deficient Brattleboro rats, unlike Wistar rats, 5-HTP treatment was without effect on the renal function parameters. In Wistar rats, injection of 5-HTP at the peak of water diuresis produced an abrogation of the diuretic response to water loading due to the increase in free water reabsorption. Plasma AVP increased from 1.2 ± 0.4 to 4.2 ± 1.6 pg/ml (n = 8 in each group, p < 0.01). Hyperosmotic treatment of Wistar rats with a 2% NaCl solution stimulated AVP secretion compared to baseline (from 3.2 ± 0.1, n = 7 to 5.6 ± 0.9, n = 7, p < 0.01), and the saluretic response developed on the background of high free water reabsorption. When injected concomitantly with NaCl solution, 5-HTP revealed no additive effect on plasma AVP and on free water reabsorption. We conclude that the 5-HTP-caused increase in brain serotonin contributed significantly to the dynamics of changes in the osmoregulatory response to the hypo-osmotic challenge due to stimulation of AVP secretion. 5-HTP had no additive effect on the osmoregulatory response to hyperosmotic loading. Peripherally injected 5-HTP had no effect on the renal function, being absent in AVP-deficient Brattleboro rats.

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“…In view of the rising popularity and wide availability of 5-HTP containing drinks, we feel that scientists and the general public alike would profit from an additional nugget of information regarding a previously unforeseen effect of 5-HTP consumption at an inappropriate time, as brought to light by recent literature in the area. 5-HTP crosses the blood -brain barrier upon systemic administration, bypasses the rate-limiting step in serotonin synthesis, elevates brain serotonin, 4 and affects non-REM sleep 5 in rodents, generally promoting wakefulness if administered at light onset, and promoting non-REM sleep with dark onset administration. In a recent study (March 2012), we investigated some of the effects 5-HTP had on the mammalian circadian system, using a nocturnal model.…”

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confidence: 99%

The 5-HTP sip tryp: a timely word to the wise

Basu¹,

Singaravel²

2013

CPT

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Recently, an editorial in Nature Neuroscience pointed out the need for exercising caution in the use of over-the-counter drinks purporting to promote relaxation and containing, among other substances with chronobiotic activity, L-5-Hydroxytryptophan (5-HTP).1 This reality-check certainly raises an issue worth the attention of scientists who deal with, and laymen who dabble in, biological rhythms. Proprietary and patented formulations often project an image of safety, which is augmented by their over-thecounter availability as attractively packaged nutritional supplements. The allure of these bottled shots of bliss may seem undeniable to the general public. An online search of the words "5-HTP relaxation drink" returns . 7 million websites. Websites promoting these drinks do carry limited warnings or disclaimers (in fine print). The actual concentration of constituents is sometimes not provided in the online information leaflets. Certain websites provide a Natural Standard Editorial Board blinded review, 2,3 which summarizes known scientific literature (exhaustively) and mentions likely safe doses. In view of the rising popularity and wide availability of 5-HTP containing drinks, we feel that scientists and the general public alike would profit from an additional nugget of information regarding a previously unforeseen effect of 5-HTP consumption at an inappropriate time, as brought to light by recent literature in the area. 5-HTP crosses the blood -brain barrier upon systemic administration, bypasses the rate-limiting step in serotonin synthesis, elevates brain serotonin, 4 and affects non-REM sleep 5 in rodents, generally promoting wakefulness if administered at light onset, and promoting non-REM sleep with dark onset administration. In a recent study (March 2012), we investigated some of the effects 5-HTP had on the mammalian circadian system, using a nocturnal model. 6 In nocturnal mice, 5-HTP causes phase advances during the mid-subjective day, phase delays during the mid-subjective night and, at certain other times, ambiguous or no apparent phase-shifting effects at all. In this paper, we had expressed concern regarding the potentially detrimental effects caused by temporally inappropriate administration of 5-HTP, especially in cases where the circadian system has been previously subjected to a stressor, for example jet lag, and this is a caveat not mentioned by many, or perhaps any, marketers of these products. Additionally, experiments conducted at our lab using nocturnal field mice 7 indicate that 5-HTP administered in the late subjective night, when combined with light, may actually transiently increase locomotor activity, along with increasing light-induced phase shifts, through possibly arousal-dependent mechanisms most likely involving Dovepress submit your manuscript | www.dovepress.com

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The effect of oral 5-HTP administration on 5-HTP and 5-HT immunoreactivity in monoaminergic brain regions of rats

Cited by 57 publications

References 24 publications

Oral administration of 5‐hydroxytryptophan (5‐HTP) impairs decision making under ambiguity but not under risk: evidence from the Iowa Gambling Task

Oral administration of 5‐hydroxytryptophan (5‐HTP) impairs decision making under ambiguity but not under risk: evidence from the Iowa Gambling Task

Effect of an Increase in Brain Serotonin on the Osmoregulatory Response to a Hypo- or Hyperosmotic Load in Wistar and Vasopressin-Deficient Brattleboro Rats

The 5-HTP sip tryp: a timely word to the wise

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