Serotonin (5-HT) precursor loading with 5-hydroxy-l-tryptophan (5-HTP) reduces locomotor activation produced by (+)-amphetamine in the rat

Baumann, Michael H.; Williams, Zakia; Żółkowska, Dorota; Rothman, Richard B.

doi:10.1016/j.drugalcdep.2010.09.015

Cited by 17 publications

(26 citation statements)

References 42 publications

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“…It is reported that low levels of 5-HTP supplementation (Յ10 mg 5-HTP/kg body wt/day) does not alter 5-HTP metabolites in blood and tissues (8,58). Consistent with this, 5-HTP supplementation for mice in Fig.…”

Section: -Htp Diets Did Not Alter Total Tissue Levels Of 5-htp and Isupporting

confidence: 66%

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Inhibition of allergic inflammation by supplementation with 5-hydroxytryptophan

Abdala-Valencia¹,

Berdnikovs²,

McCary³

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Clinical reports indicate that patients with allergy/asthma commonly have associated symptoms of anxiety/depression. Anxiety/depression can be reduced by 5-hydroxytryptophan (5-HTP) supplementation. However, it is not known whether 5-HTP reduces allergic inflammation. Therefore, we determined whether 5-HTP supplementation reduces allergic inflammation. We also determined whether 5-HTP decreases passage of leukocytes through the endothelial barrier by regulating endothelial cell function. For these studies, C57BL/6 mice were supplemented with 5-HTP, treated with ovalbumin fraction V (OVA), house dust mite (HDM) extract, or IL-4, and examined for allergic lung inflammation and OVA-induced airway responsiveness. To determine whether 5-HTP reduces leukocyte or eosinophil transendothelial migration, endothelial cells were pretreated with 5-HTP, washed and then used in an in vitro transendothelial migration assay under laminar flow. Interestingly, 5-HTP reduced allergic lung inflammation by 70-90% and reduced antigen-induced airway responsiveness without affecting body weight, blood eosinophils, cytokines, or chemokines. 5-HTP reduced allergen-induced transglutaminase 2 (TG2) expression and serotonylation (serotonin conjugation to proteins) in lung endothelial cells. Consistent with the regulation of endothelial serotonylation in vivo, in vitro pretreatment of endothelial cells with 5-HTP reduced TNF-α-induced endothelial cell serotonylation and reduced leukocyte transendothelial migration. Furthermore, eosinophil and leukocyte transendothelial migration was reduced by inhibitors of transglutaminase and by inhibition of endothelial cell serotonin synthesis, suggesting that endothelial cell serotonylation is key for leukocyte transendothelial migration. In summary, 5-HTP supplementation inhibits endothelial serotonylation, leukocyte recruitment, and allergic inflammation. These data identify novel potential targets for intervention in allergy/asthma.

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Section: -Htp Diets Did Not Alter Total Tissue Levels Of 5-htp and Isupporting

confidence: 66%

“…1B). The 5-HTP in this diet is about fivefold lower than the 5-HTP concentrations reported to increase systemic serotonin, increases serotonin-mediated intestinal peristalsis, and induces diarrhea in mice (8,14,19,58,99). 5-HTP supplementation as in Fig.…”

Section: -Htp Reduces Lung Inflammation Inmentioning

confidence: 92%

Inhibition of allergic inflammation by supplementation with 5-hydroxytryptophan

Abdala-Valencia¹,

Berdnikovs²,

McCary³

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Although no mixed DA/5-HT releasers are clinically available at the present time, a viable treatment approach might be to administer a DA releaser in conjunction with a serotonergic medication. Examples of this combination strategy include the use of the (ϩ)-amphetamine with the 5-HT precursor L-5-hydroxytryptophan Baumann et al, 2010). A similar combination, phentermine and L-5-hydroxytryptophan, is being used in humans to treat obesity (Hendricks et al, 2009;Rothman, 2010).…”

Section: Discussionmentioning

confidence: 99%

In Vivo Effects of Amphetamine Analogs Reveal Evidence for Serotonergic Inhibition of Mesolimbic Dopamine Transmission in the Rat

Baumann

Clark²,

Woolverton³

et al. 2011

The Journal of Pharmacology and Experimental Therapeutics

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101

120

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Evidence suggests that elevations in extracellular serotonin (5-HT) in the brain can diminish stimulant effects of dopamine (DA). To assess this proposal, we evaluated the pharmacology of amphetamine analogs (m-fluoroamphetamine, p-fluoroamphetamine, m-methylamphetamine, p-methylamphetamine), which display similar in vitro potency as DA releasers (EC 50 ϭ 24 -52 nM) but differ in potency as 5-HT releasers (EC 50 ϭ 53-1937 nM). In vivo microdialysis was used to assess the effects of drugs on extracellular DA and 5-HT in rat nucleus accumbens, while simultaneously measuring ambulation (i.e., forward locomotion) and stereotypy (i.e., repetitive movements). Rats received two intravenous injections of drug, 1 mg/kg at time 0 followed by 3 mg/kg 60 min later. All analogs produced dose-related increases in dialysate DA and 5-HT, but the effects on DA did not agree with in vitro predictions. Maximal elevation of dialysate DA ranged from 5-to 14-fold above baseline and varied inversely with 5-HT response, which ranged from 6-to 24-fold above baseline. All analogs increased ambulation and stereotypy, but drugs causing greater 5-HT release (e.g., p-methylamphetamine) were associated with significantly less forward locomotion. The magnitude of ambulation was positively correlated with extracellular DA (p Ͻ 0.001) and less so with the ratio of DA release to 5-HT release (i.e., percentage DA increase divided by percentage 5-HT increase) (p Ͻ 0.029). Collectively, our findings are consistent with the hypothesis that 5-HT release dampens stimulant effects of amphetamine-type drugs, but further studies are required to address the precise mechanisms underlying this phenomenon.

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“…In contrast, 5-HTP increases extracellular serotonin levels independent of the rate of tryptophan uptake. Indeed, a previous study demonstrated that 5-HTP administration increased brain 5-HT levels at a similar dose to that used in the present study (15).…”

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confidence: 85%