Treatment of menopausal hot flashes with 5-hydroxytryptophan

Objective

Much recent research has focused on nonhormonal treatments for menopausal hot flashes. The purpose of the present study was to determine the effects of 5-hydroxytroptophan (5-HTP), the immediate precursor of serotonin, upon menopausal hot flashes. Selective, serotonergic, reuptake inhibitors (SSRIs), which increase the amount of serotonin in the synaptic gap, have shown some promise in the amelioration of hot flashes.

Methods

We administered 5-HTP or placebo, in double-blind fashion, to 24 postmenopausal women reporting frequent hot flashes. Treatment outcome was measured using a miniature, electronic, hot flash recorder.

Results

No significant effects of 150 mg/day 5-HTP upon hot flash frequency were found. The 5-HTP group had 23.8 ± 5.7 (SD) hot flashes/24 h prior to treatment and 18.5 ± 9.6 at the end of treatment. The placebo group had 18.5 ± 9.6 before treatment and 22.6 ± 12.4 at treatment completion.

Conclusions

At the dose given, 5-HTP does not significantly ameliorate frequency of menopausal hot flashes, as measured objectively with an electronic recorder. Given the small size, this study must be considered preliminary in nature.     

The role of 5-hydroxytryptophan (5-HTP) in the regulation of the sleep/wake cycle in parachlorophenylalanine (p-CPA) pretreated rat: a multiple approach study

Summary In the rat, the insomnia which follows the administration of parachlorophenylalanine (p-CPA), a serotonin synthesis inhibitor, is transiently reversed either by intra-cisternal injection of L-5-HTP or by an associated injection of 5-HTP and an L-aromatic-aciddecarboxylase inhibitor (benserazide). Histochemical, immunohistochemical and chemical investigations showed that 5-HTP administration does not lead to a detectable increase in cerebral 5-HT. These findings suggest that the restoration of sleep after p-CPA treatment could be mediated by the central action of 5-HTP.     

Mast Cells and 5-HT: Uptake of labelled 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan in relation to storage of 5-HT in individual rat mast cells

The capacity of individual rat peritoneal mast cells to take up and concentrate radioactively labelled 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP) was studied by quantitative cyto-chemical methods. By means of consecutive application of microfluorometric, autoradiographic and microinterferometric methods, the following parameters could be determined for each cell: 1. Relative amount of endogenous 5-HT. 2. Concentration of accumulated isotopes. 3. Dry mass. 4. Concentration of endogenous 5-HT. 5. Total amount of accumulated isotopes. The calculated correlations of these variables to each other showed general heterogeneity of the population, variations between the different cells being very large. However, on the whole, increasing dry mass of the mast cells was accompanied by an increase in 5-HT content, but with a decrease in concentrations of endogenous 5-HT and accumulated radioactive 5-HTP. Similarly, cells having large stores of endogenous 5-HT showed a higher total uptake, but a lower cellular concentration of exogenous 5-HT and 5-HTP, than cells that were poor in endogenous 5-HT. The results indicated that the uptake of ³H-5-HTP was proportional to the total area of the cell membrane, while the degree of 3-HT uptake was determined by other factors. When the concentrations of radioactivity in the incubation medium was compared to that of the living mast cell, it was found that the averagr cell was able to concentrate exogenous 5-HTP and 5-HT around 4 and 30 times, respectively.     

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

5-Hydroxytryptophan (5-HTP), which is the rate-limiting precursor in serotonin (5-hydroxytryptamine (5-HT)) biosynthesis, is used as an oral supplement to enhance serotonin levels in humans. To evaluate its effects on serotonin levels and localization, 5-hydroxytryptophan was administered to Sprague-Dawley rats either orally or via intraperitoneal injection. 5-Hydroxytryptophan-immunoreactivity was co-localized with serotonin-immunoreactivity in the serotonergic dorsal raphe nucleus of control animals and this was not changed in animals given 5-hydroxytryptophan. Oral 5-HTP administration increased the intensity of both 5-HTP and serotonin immunoreactivity in raphe neurons. However, 5-HTP treatment also caused ectopic 5-hydroxytryptophan-immunoreactivity and serotonin-immunoreactivity in normally dopaminergic neurons of the substantia nigra par compacta. Serotonin-immunoreactivity was confined to neurons that also displayed amino acid decarboxylase immunoreactivity, but in a small percentage of substantia nigra neurons, serotonin immunoreactivity was not co-localized with tyrosine hydroxylase-immunoreactivity. The intensity of the immunoreactivity to serotonin and 5-hydroxytryptophan in the substantia nigra was maximal within 2h of 5-hydroxytryptophan administration and returned to control levels by 24h. This time course mirrored changes in HPLC measurements of 5-hydroxytryptophan, serotonin, and the metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the urine. 5-Hydroxytryptophan administration did not cause ectopic appearance of either serotonin or 5-hydroxytryptophan in the noradrenergic locus coeruleus. These results suggest that a single oral dose of 5-HTP increases the 5-HTP and serotonin content of serotonergic neurons and causes the transient ectopic appearance of serotonin in some normally non-serotonergic neurons.     

Adenosine deaminase-containing hypothalamic neurons accumulate 5-hydroxytryptophan: a dual-colour immunofluorescence procedure using a new fluorescence marker

Neurons of the posterior hypothalamic magnocellular nucleus (PHMN) in the rat are immunoreactive for adenosine deaminase (ADA) and cells coextensive with this nucleus show immunoreactivity for serotonin after pretreatment with 5-hydroxytryptophan (5-HTP). The degree to which ADA coexists in cells having 5-HTP uptake capability was analyzed by a new double immunohistofluorescence procedure employing diethylaminocoumarin (DAMC). It was determined that 5-HTP accumulating cells of the PHMN represent a subpopulation of those immunoreactive for ADA. These results add further to the neurochemical characterization of this globally projecting hypothalamic cell group and point out the utility of DAMC as a new immunohistofluorescence marker.     

On the presence of serotonin in the gut lumen and possible release mechanisms

The possible presence of a luminal release of serotonin (5-HT) from gut enterochromaffin cells (EC) of the rat. was studied after the injection of the tritiated 5-HT precursor 5-hydroxytryptophan [³H]-5-HTP by electron microscopic autoradiography. The uptake of 5-HTP into gut epithelial cells was also studied by fluorescence histochemistry according to the Hillarp-Falck technique at the same post-injection interval as in the autoradiography experiments. 3 h after the injection of 5-HTP (100 mg/kg i. v.) the fluorescence intensity of EC was increased and numerous, probably enteroendocrine, cells had an increased yellow tryptamine induced fluorescence due to an uptake of 5-HTP and probably decarboxylation to 5-HT. However, the labelled precursor [³H]-5-HTP was taken up not only into granules of enteroendocrine cells but also incorporated into the cytoplasm and nucleus of nonendocrine cells when studied by autoradiography. After 10 min of efferent electrical stimulation of the vagal nerve much of the label was found in the gut lumen suggesting a release of the amine. The hypothesis of a luminal release of 5-HT was further corroborated in starved cats, where considerable amounts of 5-HT were detected by fluorimetric assays in the lumen of isolated jejunal loops under resting conditions. The experiments demonstrate that: (i) 5-HTP is taken up not only into typical EC but also into other enteroendocrine cells, and most probably decarboxylated to 5-HT. (ii) Also intestinocytes take up [³H]-5-HTP and incorporate the amino acid into peptides to a certain extent, (iii) Following vagal nerve stimulation labelled material, probably 5-HT, is secreted into the gut lumen, (iv) 5-HT normally occurs in the gut lumen.     

Effects of L-DOPA and L-5-HTP on the visual evoked response

Small doses (10 and 20 mg/kg) of L-DOPA inhibited the amplitude of the visual evoked response (VER), while large doses (40 and 80 mg/kg) enhanced it. Though low doses (12.5 and 25 mg/kg) of L-5-HTP caused a slight increase in amplitude of the VER, the simultaneous administration of 12.5 mg/kg of L-5-HTP and 10 mg/kg of L-DOPA produced a marked enhancement. The peak latency was prolonged after the injection of any doses of L-DOPA, L-5-HTP, or both.     

Evaluation of the 5-hydroxytryptamine receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin in different rodent models of epilepsy

The effects of the serotonin (i.e. 5-hydroxytryptamine; 5-HT) S1 receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and the 5-HT precursor L-5-hydroxytryptophan (5-HTP) were compared in different models of epilepsy. 5-HTP significantly increased the threshold for electroconvulsions and pentylenetetrazol-induced seizures in mice and rats but exerted no anticonvulsant effects in epileptic gerbils and amygdaloid-kindled rats. The anticonvulsant effect of 5-HTP against electroconvulsions in rats could be attenuated by the S2 receptor antagonist, ketanserin. 8-OH-DPAT displayed no anticonvulsant effects in the seizure models examined but gave rise to proconvulsant effects in mice. Differences between 5-HTP and 8-OH-DPAT were also observed in terms of behavioural changes in response to both drugs. The data indicate that S2 receptors may be involved in the anticonvulsant effect of 5-HTP.     

Alpha 2-adrenoceptor modulation of 5-HT biosynthesis in the rat brain.

The purpose of the present study is to clarify the modulation of the biosynthesis of serotonin (5-HT) via the alpha 2-adrenoceptors in the brain. For this purpose, 5-hydroxytryptophan (5-HTP) accumulation was determined using an HPLC-ECD system in the presence of the inhibition of aromatic L-amino acid decarboxylase. Administration of alpha 2-adrenoceptor agonist, clonidine, produced a reduction of the in vivo 5-HTP accumulation in both the rat hippocampus and dorsal raphe nucleus. In addition, alpha 2-adrenoceptor antagonist, idazoxan, increased the 5-HTP accumulation in both the hippocampus and the dorsal raphe nucleus. In rats with catecholaminergic neurons denervated by pretreatment with 6-hydroxydopamine, clonidine failed to produce a reduction of 5-HTP accumulation in the dorsal raphe nucleus. On the other hand, hippocampal 5-HTP accumulation was decreased significantly. Brain tryptophan levels were unaffected by either clonidine or idazoxan. These results suggest that alpha 2-adrenoceptors might modulate serotonin biosynthesis and this modulation might be related to the neuroanatomical differences in the rat brain.     

运动应激对大鼠胃肠道5-HT免疫反应细胞的影响

目的　探讨力竭游泳对大鼠胃肠道 5 HT免疫反应细胞 (5 HTIR细胞 )的影响。方法　本研究以力竭游泳大鼠为运动模型 ,游泳后即刻取大鼠胃窦、十二指肠、空肠和回肠用免疫组织化学SP法检测 5 HT ,用图像分析系统测定胃肠 5 HTIR细胞数和平均灰度。结果　 (1)游泳后胃窦 5 HTIR细胞数虽与对照组无明显差异 ,但阳性细胞的平均灰度却明显下降 (P <0 .0 5)。 (2 )十二指肠、空肠、回肠 5 HTIR细胞数都明显下降 ,与对照组相比有显著性差异 (P <0 .0 5) ,但只有空肠 5 HTIR细胞平均灰度明显增加 ,与对照组间有明显差异 (P <0 .0 5)。结果　胃肠道不同区域 5 HTIR细胞以不同的反应方式应答运动应激。     

Quinpirole--a 5-HT receptor antagonist?

The rate of brain monoamine synthesis was estimated in the rat by measuring the accumulation of dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) following inhibition of cerebral aromatic amino acid decarboxylase by NSD-1015 (475 mumol/kg, i.p., 30 min before decapitation). As expected, pretreatment with reserpine, (8.2 mumol/kg, s.c., -18 h) produced a marked and statistically significant increase in the DOPA accumulation in the ventral striatum and in the neocortex, whereas only minor changes were noted in 5-HTP accumulation in the same brain areas. The administration of terguride or quinpirole (30 mumol/kg, s.c., -65 min) resulted in both cases in an antagonism of the reserpine-induced increase in the DOPA accumulation. The effect was less marked in the neocortex than in the ventral striatum, but there was no difference between the effects produced by either compound. In contrast, the two drugs produced opposite effects on the 5-HTP accumulation in the ventral striatum as well as in the neocortex. Thus, there was a decrease and an increase in the 5-HTP accumulation by terguride and quinpirole administration, respectively. Together the results suggest that, in the reserpine treated rat, both terguride and quinpirole to the same degree stimulate dopamine receptors in the ventral striatum and noradrenaline receptors in the neocortex. To the extent that serotonin receptors in these two brain areas mediate the effects on 5-HTP accumulation of terguride and quinpirole, respectively, these receptors appear differently affected by the two compounds: stimulation by terguride and blockade by quinpirole.     

5-HTP hypothesis of schizophrenia

Introduction and aims

To pose a new hypothesis of schizophrenia that affirms and unifies conventional hypotheses.

Methods

Outside the brain, there are 5-HTP-containing argyrophil cells that have tryptophan hydroxylase 1 without l-aromatic amino acid decarboxylase. Monoamine oxidase in the liver and lung metabolize 5-HT, rather than 5-HTP, and 5-HTP freely crosses the blood–brain barrier, converting to 5-HT in the brain. Therefore I postulate that hyperfunction of 5-HTP-containing argyrophil cells may be a cause of schizophrenia. I investigate the consistency of this hypothesis with other hypotheses using a deductive method.

Results

Overactive 5-HTP-containing argyrophil cells produce excess amounts of 5-HTP. Abundant 5-HTP increases 5-HT within the brain (linking to the 5-HT hypothesis), and leads to negative feedback of 5-HT synthesis at the rate-limiting step catalysed by tryptophan hydroxylase 2. Owing to this negative feedback, brain tryptophan is further metabolized via the kynurenine pathway. Increased kynurenic acid contributes to deficiencies of glutamate function and dopamine activity, known causes of schizophrenia.

Conclusions

The 5-HTP hypothesis affirms conventional hypotheses, as the metabolic condition caused by acceleration of tryptophan hydroxylase 1 and suppression of tryptophan hydroxylase 2, activates both 5-HT and kynurenic acid. In order to empirically test the theory, it will be useful to monitor serum 5-HTP and match it to different phases of schizophrenia. This hypothesis may signal a new era with schizophrenia treated as a brain–gut interaction.     

Effects of serotonergic activation by 5-hydroxytryptophan on sleep and body temperature of C57BL/6J and interleukin-6-deficient mice are dose and time related

STUDY OBJECTIVES: Extensive data implicate serotonin (5-hydroxytryptamine [5-HT]) in the regulation of sleep. Jouvet has hypothesized that 5-HT promotes wakefulness, yet is necessary for subsequent non-rapid eye movement (NREM) sleep, actions he proposes to be mediated by sleep factors. Studies in rat support this dual role for 5-HT. The objectives of this study were to (1) determine effects of serotonergic activation on sleep of mice and (2) elucidate a potential role for the cytokine interleukin-6 as a sleep factor mediating serotonergic effects on sleep. DESIGN: C57BL/6J and B6.129S6-II6(tm1Kopf)(interleukin-6 knockout [IL-6 KO]) mice were purchased from the Jackson Laboratory and instrumented for recording the electroencephalogram and body temperature. After recovery, separate groups of mice were injected intraperitoneally at either light or dark onset with vehicle or with the 5-HT precursor 5-hydroxytryptophan (5-HTP). Sleep-wake behavior was determined and body temperature recorded for 24 hours after injections. RESULTS: 5-HTP induced hypothermia in both mouse strains. When injected at dark onset, the highest dose of 5-HTP (200 mg/kg) increased NREM sleep. Light onset administration initially increased wakefulness, with increases in NREM sleep apparent only during the subsequent dark period. For most parameters, there were no differences in responses between strains. However IL-6 KO mice at some doses exhibited a greater increase in NREM sleep. CONCLUSIONS: 5-HTP alters sleep-wake behavior and body temperature of mice in a manner similar to that of rats. Increases in NREM sleep after 5-HTP are apparent only during the dark period, which may represent a fundamental property of the serotonergic system. These results suggest that 5-HT should not be considered either wake promoting or NREM sleep promoting. Rather, the role of 5-HT in the regulation of sleep-wake behavior must be considered within the context of the degree to which the system is activated and the time at which the activation occurs.     

Effects of Repeated Administration of Pilocarpine and Isoproterenol on Aquaporin-5 Expression in Rat Salivary Glands

Aquaporins are water channel proteins which enable rapid water movement across the plasma membrane. Aquaporin-5 (AQP5) is the major aquaporin and is expressed on the apical membrane of salivary gland acinar cells. We examined the effects of repeated administration of pilocarpine, a clinically useful stimulant for salivary fluid secretion, and isoproterenol (IPR), a stimulant for salivary protein secretion, on the abundance of AQP5 protein in rat salivary glands by immunofluorescence microscopy and semi-quantitative immunoblotting. Unexpectedly AQP5 was decreased in pilocarpine-administered salivary glands, in which fluid secretion must be highly stimulated, implying that AQP5 might not be required for fluid secretion at least in pilocarpine-administered state. The abundance of AQP5, on the other hand, was found to be significantly increased in IPR-administered submandibular and parotid glands. To address the possible mechanism of the elevation of AQP5 abundance in IPR-administered animals, changes of AQP5 level in fasting animals, in which the exocytotic events are reduced, were examined. AQP5 was found to be decreased in fasting animals as expected. These results suggested that the elevation of cAMP and/or frequent exocytotic events could increase AQP5 protein. AQP5 expression seems to be easily changed by salivary stimulants, although these changes do not always reflect the ability in salivary fluid secretion.     

培养脊髓神经元中微管相关蛋白5的表达

目的　探讨初代培养脊髓神经元中微管相关蛋白 (MAP5 )的表达特征及其调节因素。方法　应用荧光免疫细胞化学检测初代培养脊髓神经元中MAP5的表达。结果　MAP5在培养脊髓神经元中呈网状分布在胞浆及突起中。诺考达唑引起微管解聚及MAP5的结构破坏 ,荧光物质分布不均匀 ,突起呈串珠或断裂。PMA(phorbol 12 myristate 13 acetate)能诱发微管及MAP5聚合 ,胞浆中荧光物质呈疏松的网状结构。结论　MAP5在初代培养脊髓神经元胞浆及突起中明显表达 ,且表达受微管解聚剂诺考达唑及微管聚合剂PMA的调控。     

Cerebrovascular serotonergic receptors mediating vasoconstriction: further evidence for the existence of 5-HT2 receptors in rat and 5-HTVIike receptors in guinea-pig basilar arteries

Pharmacological experiments were carried out on isolated basilar arteries (BA) from the brain vasculature of guinea-pig and rat in order to characterize post-junctional serotonergic receptors mediating contraction by the use of selective agonists and antagonists. The sensitivity to 5-HT was higher, but the intrinsic activity lower, in guinea-pig compared to rat vessels. The contractile potency of the 5-HT₁ agonist, 5-carboxamidotryptamine (5-CT), was three times higher than 5-HT in guinea-pig but 16 times lower in rat BA. In arteries from both species the 5-HT_1A agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), only caused weak contraction. In rat BA, where the serotonergic contractile receptors are ketanserin-sensitive, mesulergine inhibited the contraction in doses high enough to block 5-HT₂ receptors, and also propranolol slightly inhibited the contraction, probably due to its binding to these receptors. Methiothepin, a potent antagonist of the 5-HT₁-like receptors, affected the contraction in a non-competitive manner. The antagonist profile was different in guinea-pig BA: propranolol was ineffective, mesulergine caused a slight, non-surmountable inhibition, whereas methiothepin acted as a true, competitive antagonist. The data support previous suggestions that the serotonergic contraction in rat BA is mediated by 5-HT₂ receptors, whereas the present data show that 5-HT₁-like receptors predominate in guinea-pig BA.     

Tryptophan, 5-HTP, 5-HT and 5-HIAA in the cerebrospinal fluid and sexual behavior in male rats

No changes were found in the concentration of tryptophan (Trp), 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT) or 5-hydroxyindole acetic acid (5-HIAA) in the cerebrospinal fluid (CSF) of male rats either before sexual activity, immediately after ejaculation of after the postejaculatory refractory period (PEI). Injection of the Trp hydroxylase inhibitor p-chlorophenylalanine (PCPA, 25 or 100 mg/kg i.p. for 3 days) in combination with an injection of the monoamine oxidase inhibitor pargyline (100 mg/kg i.p.) increased the concentration of Trp while decreasing the concentration of 5-HTP, 5-HT and 5-HIAA in the CSF. Furthermore 100 (but not 25) mg/kg PCPA in combination with pargyline caused a significant reduction in the latency to ejaculation. Injection of probenecid (200 mg/kg i.p.), an inhibitor of the transport of 5-HIAA from the CSF, increased the concentration of 5-HIAA in the CSF and slightly prolonged the latency to ejaculation. Sexual activity caused no further increase in CSF 5-HIAA levels in the probenecid-treated rats. Since drug-induced changes in sexual behavior are associated with marked alterations in 5-HT metabolism in the CSF, whereas the changes in the behavior which occur normally are not, these results question the physiological significance of the proposed inhibitory role of 5-HT in male rat sexual behavior.     

人胎儿结肠及直肠内胰岛淀粉样多肽及5-羟色胺免疫反应细胞的研究

目的 探讨胰岛淀粉样多肽(IAPP)在人胎结肠、直肠中的个体发生及其与其他生物活性物质的关系。方法 用免疫组织化学SABC法，对31例9～27周人胎结肠及直肠中IAPP免疫反应(IR)细胞和5-羟色胺(5-HT)-IR细胞进行定位研究。结果 人胎9周结肠内已可见较多的5-HT-IR细胞，而IAPP-IR细胞于18周出现，直肠内5-HT-IR细胞和IAPP-IR细胞均于11周出现。随胎龄增长，5-HT-IR细胞由少至多，20周达到高峰，21周后逐渐减少；而IAPP-IR细胞在整个胎期始终分散存在，数量较少。经邻片比较观察发现，IAPP-IR细胞与部分5-HT-IR细胞定位一致。免疫组织化学双染法显示有的细胞内IAPP与5-HT共存。结论 胎儿期结肠及直肠的内分泌细胞已开始合成IAPP，并在部分细胞内IAPP和5-HT有共存。     

Establishment of stable multiple myeloma cell line with overexpressed PDCD5 and its proapoptosis mechanism

Objective: The transfected multiple myeloma cell line showing a stable doxycycline (DOX)-induced expression of PDCD5 was established. PDCD5 overexpression in the transfected cell line was analyzed for its effect on the dexamethasone (DXM)-induced apoptosis along with a discussion on the mechanism. Methods: (1) Lentiviral plasmid was used for the transfection of PDCD5 gene into the multiple myeloma cells. The screening was done by applying puromycin, and PDCD5 expression was induced by DOX. Real-time fluorescence quantitative PCR and Western Blot were performed to detect the expression levels of the target gene in the stable transfection group and the empty vector group; (2) The cell apoptosis rates of stable transfection group, blank group and empty vector group were measured by Annexin-APC/PI double staining flow cytometry; (3) Real-time fluorescence quantitative PCR and Western Blot were carried out to detect the expression levels of survivin, casepase-3 and Bcl-2 genes and proteins. Results: PDCD5 expression was significantly increased in the stably tranfected multiple myeloma cells compared with blank group and empty vector group. The cells in the transfection group were more sensitive to DXM, and the proportion of apoptotic cells was obviously higher than that of the blank group and the empty vector group (P<0.05). Survivin and Bcl-2 were considerably downregulated in U266/PDCD5 cells and combined DXM group than in the single agent group. However, caspase-3 was significantly upregulated. Conclusion: Multiple myeloma cell line transfected with endogenous PDCD5 gene was established. The endogenous PDCD5 overexpression accelerated the cell apoptosis under DXM induction. The proapoptotic action of PDCD5 gene had the effect of activating casepase-3 and downregulating survivin and Bcl-2, which further promoted the apoptosis of multiple myeloma cells.     

Regional central serotonin receptor binding in rats treated chronically with high-dose 5-hydroxy-L-tryptophan

Summary The serotonin (5-HT) precursor 5-hydroxy-L-tryptophan (L-5-HTP) exerted differential regional effects on central 5-HT receptors in rats treated chronically by intraperitoneal injections of large incremental doses (50–200 mg/kg). There were significant reductions in B_max of agonist-labelled (-35%) and antagonist-labelled (-20%) 5-HT₂ sites in cortex but no changes in brainstem. K_d and n_H were unaffected by L-5-HTP. B_max of 5-HT₁ sites (unsubtyped) was reduced 16% in cortex and 18% in spinal cord, but the changes were not significant. Brainstem 5-HT₁ sites were unaffected. Studies at a single isotope concentration in other regions revealed significant reductions of antagonist-labelled 5-HT₂ specific binding in diencephalon (-26%) but not septum, and of 5-HT₁ binding in diencephalon (-25%) and cerebellum (-30%) but not in hippocampus or striatum. Absence of L-5-HTP-evoked changes in 5-HT receptors in brainstem may have implications for L-5-HTP-responsive and brainstem-mediated human myoclonic disorders.