A photonic atom probe coupling 3D atomic scale analysis with in situ photoluminescence spectroscopy.

Laser enhanced field evaporation of surface atoms in laser-assisted Atom Probe Tomography (APT) can simultaneously excite photoluminescence in semiconductor or insulating specimens. An atom probe equipped with appropriate focalization and collection optics has been coupled with an in situ micro-photoluminescence (µPL) bench that can be operated during APT analysis. The photonic atom probe instrument we have developed operates at frequencies up to 500 kHz and is controlled by 150 fs laser pulses tunable in energy in a large spectral range (spanning from deep UV to near IR). Micro-PL spectroscopy is performed using a 320 mm focal length spectrometer equipped with a CCD camera for time-integrated and with a streak camera for time-resolved acquisitions. An example of application of this instrument on a multi-quantum well oxide heterostructure sample illustrates the potential of this new generation of tomographic atom probes.

Transport of indirect excitons in ZnO quantum wells.

We report on spatially- and time-resolved emission measurements and observation of transport of indirect excitons in ZnO/MgZnO wide single quantum wells.

HIV/AIDS prevalence among South African health workers.

INTRODUCTION: Studies on HIV prevalence among health workers usually focus on occupational exposure to HIV. Little is known about HIV prevalence in this group. However, it is expected that HIV prevalence among health workers will reflect prevalence in their society. OBJECTIVE: To determine HIV prevalence among South African health workers. METHOD: A stratified cluster sample was drawn of 5% of health facilities in South Africa (N = 222) representative of the public and private health sectors in South Africa. The sample was designed to obtain a nationwide representative sample of medical professionals and non-professional health workers. A subsample comprising health workers in four provinces was tested for HIV status. The Orasure HIV-1 device in combination with the Vironostika HIV UNI-Form II plus O enzyme-linked immunosorbent assay (ELISA) kits were used to collect oral fluid specimens for HIV testing. RESULTS: Based on a sample of 721 health workers and a response rate of 82.5% (or 595 respondents), the study found that an estimated 15.7% (95% confidence interval (CI): 12.2-19.9%) of health workers employed in the public and private health facilities located in four South African provinces, were living with HIV/AIDS in 2002. Among younger health workers, the risk is much higher. This group (aged 18-35 years) had an estimated HIV prevalence of 20% (95% CI: 14.1-27.6%). Non-professionals had an HIV prevalence of 20.3%, while professionals had a prevalence of 13.7%. CONCLUSION: HIV prevalence among health workers in South Africa is high; this calls for the introduction of antiretroviral programmes targeting them. In addition, there is a need for the development of new policy regarding placement of infected health workers in tuberculosis (TB) wards, coupled with vigorous human resource planning to replace the health workers likely to die from AIDS. Infection control procedures also need to be reviewed.

Behavioural responses of South African youth to the HIV/AIDS epidemic: a nationwide survey.

South Africa is reported to have the largest number of people living with HIV/AIDS in the world. The present study investigated the behavioural responses of South African youth to the HIV/AIDS epidemic. A multi-stage stratified cluster sample of 2,430 youths aged 15-24 was selected, 46.9% of them males and 53.1% females. Nurses administered questionnaires to consenting youths, measuring behavioural risks and also took an oral fluid specimen for HIV antibody testing. It was found that the median age of sexual debut for both sexes was 16.5 years; most of the youths were sexually experienced with no variation by sex; sexual experience was highest among Africans living in informal urban areas; partner turnover was low and multiple partners were more common among African males living in urban informal settings; sexual frequency among sexually active youth was relatively low; secondary abstinence during the past 12 months was 24%; condom use at last sexual intercourse was high, at 52.8% for males and 47.6% for females, especially among Africans living in urban informal settings; and the majority of youths (74%) indicated that they had discussed HIV prevention with their partners during the past 12 months. These results suggest that South African youth are heeding the message to abstain, be faithful and use a condom; messages that are at the core of South Africa's HIV/AIDS prevention programme.

Differential adaptation of brain 5-HT1A and 5-HT1B receptors and 5-HT transporter in rats treated chronically with fluoxetine.

Quantification of receptor binding sites and their encoding mRNAs, and electrophysiological recordings, were used to assess central serotonin (5-HT) neurotransmission in rats 24 h after a 2-3 week treatment with the selective 5-HT reuptake inhibitor fluoxetine (8 mg/kg i.p., daily). Binding studies showed that this treatment affected neither 5-HT1A nor 5-HT1B binding sites in all brain areas examined. However, a significant decrease (-38%) in 5-HT1A mRNA levels in the anterior raphe area (but not forebrain regions) and increases in 5-HT1B mRNA levels in the striatum (+127%) and the cerebral cortex (+34%) were noted in fluoxetine-treated rats. Electrophysiological recordings in brain slices showed that chronic fluoxetine treatment reduced the potency of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin to inhibit neuronal activity in the dorsal raphe nucleus, but did not affect 5-HT1A-evoked responses of CA1 pyramidal cells in the hippocampus. These data further demonstrate that fluoxetine-induced adaptive changes in 5-HT neurotransmission exhibit marked regional differences. The decrease in 5-HT1A mRNA levels in the anterior raphe suggests that fluoxetine-induced desensitization of 5-HT1A autoreceptors involves changes at the transcription level.

Dopamine release in the nucleus accumbens and latent inhibition in the rat following microinjections of a 5-HT1B agonist into the dorsal subiculum: implications for schizophrenia.

Microinjection of a serotonergic 5-HT1B agonist (S-CM-GTNH2, 3 microg/l) into the dorsal subiculum (DS) induced long-lasting increases in dopamine (DA; +58%), dihydroxyphenylacetic acid (DOPAC; +15%) and homovanillic acid (HVA; +31%), without changing extracellular levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), measured by microdialysis in freely moving rats in the shell area of the nucleus accumbens (n. acc). Perfusion of a glutamate-N-methyl-D-aspartate (NMDA) receptor antagonist (MK 801, dizocilpine, 10 microM) through the dialysis probe in the n. acc induced similar long-lasting increases in DA and DOPAC, whereas the glutamate-quisqualate/kainate receptor antagonist (CNQX, 50 microM) had no effect. In the presence of dizocilpine in the n. acc, microinjection of S-CM-GTNH2 into the DS could still increase DOPAC and HVA, but DA levels were not further changed, whereas in the presence of CNQX, microinjection of S-CM-GTNH2 into the DS still increased not only DOPAC and HVA, but also DA levels in a way similar to that in the absence of glutamate antagonist. Therefore, activation of 5-HT1B receptors located in the DS increases the release of DA in the n. acc, presumably via the glutamatergic projection to this structure and acting through NMDA receptors in it. This implies either the suppression of a tonic indirect inhibitory influence and/or stimulation of a phasic excitatory effect of glutamate. Disruption of latent inhibition (LI) has been suggested as a model for a cognitive deficit in schizophrenia (hyperattention to irrelevant stimuli) and is usually associated with an increase in DA release in the n. acc. However, s.c. injection of RU 24 969 (0.5 mg/kg), a mixed 5-HT1A-5-HT1B agonist, which was previously shown to increase DA release in the n. acc, left LI unchanged. Moreover, bilateral microinjections of S-CM-GTNH2 into the rat DS tended to potentiate LI, in spite of the increase in DA in n. acc demonstrated here. It is concluded that not all increases in DA release in the n. acc are functionally equivalent. Sensitization of receptors or impulse-dependent increase in DA release might be necessary to disrupt LI. The possible role of altered serotonergic transmission, through h5-HT1B receptors (human homologue of the rat 5-HT1B receptors) located in the DS, in acute schizophrenia needs to be further investigated.

[Withdrawal syndrome in 2 drug addicts after intravenous injection of buprenorphine?]. / Syndrome de manque chez deux toxicomanes après injection intraveineuse de buprénorphine?

Adequate dosage of sublingual buprenorphine is now recommended for substitution treatment of severe opioid dependance. We report two cases of acute discomfort, probably linked to withdrawal syndrome, after an IV injection of high doses of buprenorphine in opiate dependant patients. Data on the pharmacokinetics and neurobiochemical aspects of buprenorphine are compared with those of other opiates. A major issue of this work is a guideline for inducing substitution treatment with this "unique" partial agonist/antagonist of endorphinic receptors.

Autoradiographic mapping of serotonin 5-HT1A, 5-HT1D, 5-HT2A and 5-HT3 receptors in the aged human spinal cord.

Quantitative autoradiography with selective radioligands was used to establish the respective distribution of serotonin 5-HT1A, 5-HT1D, 5-HT2A and 5-HT3 receptors at the cervical, thoracic and lumbar levels of the spinal cord from subjects who died at 81-94 years. A high density of 5-HT1A receptors, labeled by [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT), was found in the superficial layers of the dorsal horn, with a significant enrichment ( approximately 20%) in the lumbar vs. the thoracic and cervical segments. In contrast, only very low specific labeling by [3H]8-OH-DPAT (i.e. less than 10% of that measured in the dorsal horn), was detected in the ventral horn. 5-HT1D sites labeled by [125I]serotonin-O-carboxymethyl-glycyl-iodo-tyrosinamide ([125I]GTI) were also mainly located within the superficial layers of the dorsal horn, but no difference in their relative density was noted at the three levels of the spinal cord examined. 5-HT2A sites labeled by [3H]ketanserin were found in the dorsal horn of the cervical segments but no specific binding of this radioligand could be detected at any other level of the spinal cord of such aged subjects. Finally, a high density of [3H]S-zacopride-labeled 5-HT3 receptors was noted especially in the most superficial layer (lamina I) of the dorsal horn at all segments examined. These data provide anatomical support for a role of spinal serotonin especially in nociception processing.

5-Carboxamido-tryptamine, CP-122,288 and dihydroergotamine but not sumatriptan, CP-93,129, and serotonin-5-O-carboxymethyl-glycyl -tyrosinamide block dural plasma protein extravasation in knockout mice that lack 5-hydroxytryptamine1B receptors.

We studied the dural plasma protein extravasation response after unilateral electrical stimulation of the trigeminal ganglion in mice lacking serotonin 5-HT1B (5-HT1D beta) receptors by modifying a technique previously described in rats or guinea pigs. We investigated the inhibitory effects of six 5-HT1 receptor agonists in this model: 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (CP-93,129), sumatriptan, serotonin-5-O-carboxymethyl-glycyl -tyrosinamide (GTI), 5-methylaminosulfonylmethyl-3-(N-methylpyrrolidin-2R -ylmethyl)-1H-indole (CP-122,288), 5-carboxamido-tryptamine (5-CT), and dihydroergotamine. The plasma extravasation response did not differ between wild-type and mutant after vehicle injection. The potency of sumatriptan, CP-122,288, CP-93,129, and 5-CT in wild-type mice was similar to that previously reported for rats. CP-122,288 (1 nmol kg), 5-CT (1 nmol/kg), and dihydroergotamine (72 nmol/kg) inhibited plasma protein extravasation within dura mater after electrical trigeminal ganglion stimulation in both wild-type and knockout mice, which suggests that these agonists act predominantly via receptors other than 5-HT1B. Unlike the wild-type mice, CP-93,129 (1.4 mumol/kg), a specific 5-HT1B receptor agonist, had no effect in knockout mice. The same held true for sumatriptan (0.7 mumol/kg) and GTI (0.6 mumol/kg). These results suggest that CP-93,129, sumatriptan, and GTI exert their effects via 5-HT1B (5-HT1D beta) receptors in mice.

Modulation of dopamine release in the nucleus accumbens by 5-HT1B agonists: involvement of the hippocampo-accumbens pathway.

Changes in extracellular levels of dopamine (DA), DA metabolites DOPAC and HVA, and the serotonin metabolite 5-HIAA, were measured by microdialysis in the rat nucleus accumbens (n. acc) after treatments with serotonin (5-HT)1A (8-OH-DPAT) or 5-HT1B (RU 24969 and S-CM-GTNH2) receptor agonists. Subcutaneous injections of RU 24969 (0.02-2 mg/kg) dose-dependently decreased 5-HIAA levels (0 to -38%), and also induced long-lasting increases in DA levels (0 to +37%) and DOPAC (+11% at the dose 0.5 mg/kg) in the shell of the n. acc, whereas 8-OH-DPAT (0.25 and 0.5 mg/kg) reduced 5-HIAA levels (-25%) and very slightly increased DOPAC at the lower dose (+4%), but had no effect on DA levels. Three weeks after interruption of the subicular efferent projections, the increase in DA levels previously observed after systemic injections of RU 24969 was abolished. Microinjections of RU 24969 (10 micrograms/microliter) or S-CM-GTNH2 (3 micrograms/microliter) into the ventral subicular area reproduced the effects of systemic injections of RU 24969 cn DA levels and increased DOPAC (+13%; +19%, respectively) and HVA levels (+23%; +24%), with no significant change in 5-HIAA. It is concluded that: (1) serotonin interacts with the mesolimbic dopaminergic system through 5-HT1B, but not 5-HT1A, receptors: and (2) serotonin interaction with the mesolimbic dopaminergic system involves postjunctional 5-HT1B heteroreceptors located in the ventral subicular area, which modulate the activity of glutamatergic hippocampo-accumbens pathways and only secondarily alter DA levels in the n. acc. The possible relevance of these results for schizophrenia is discussed.

Immunolabeling of central serotonin 5-HT1D beta receptors in the rat, mouse, and guinea pig with a specific anti-peptide antiserum.

A synthetic peptide (25 amino acids) corresponding to a specific portion of the third intracytoplasmic loop of the rat serotonin 5-HT1B/1D beta receptor was coupled to keyhole limpet hemocyanin and injected monthly into rabbits. Anti-peptide antibodies were detected by enzyme-linked immunosorbent assay and characterized by immunoprecipitation of the 5-HT1B/1D beta receptor in CHAPS-solubilized extracts from rat striatal membranes. Up to 60% of solubilized striatal serotonin-O-carboxymethylglycyl[125I]iodotyrosinamide ([125I]GTI; a selective 5-HT1B/1D radioligand) binding sites were immunoprecipitated and subsequently pharmacologically identified as 5-HT1B receptors. The remaining 40% of [125I]GTI binding sites were shown to be 5-HT1D receptors. In addition, these antibodies were successfully used in immunofluorescence experiments to detect the 5-HT1B/1D beta, but not the 5-HT1D/1D alpha, receptor in transiently transfected LLC-PK1 cells. Immunoautoradiographic experiments performed with brain sections from the rat, mouse, and guinea pig showed that the substantia nigra and globus pallidus contained the highest densities of 5-HT1D beta receptor-like immunoreactivity. Comparison of the regional distribution of immunolabeling with that of the specific binding of [125I]GTI in the brain of these species further confirmed that the anti-peptide antibodies selectively recognized only the 5-HT1D beta component of [125I]GTI specific receptor binding sites.

Distractibility and locomotor activity in rat following intra-collicular injection of a serotonin 1B-1D agonist.

The superior colliculus (SC) is thought to be the decision center for reactions to novel and/or moving stimuli in the peripheral visual field. Serotonin 1B (5-HT1B) receptors were previously demonstrated to be located on collicular axon terminals of retinal ganglion cells and their activation might depress afferent inputs from the retina. The effects of intra-collicular injections of 5-HT1 drugs on distractibility were studied in hooded rats trained to run toward illuminated targets for a food reward in a 2-choice runway. 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT), a 5-HT1A receptor agonist, RU 24969, a mixed 5-HT1A and 5-HT1B agonist, serotonin-O-carboxymethylglycyltyrosinamide (S-CM-GTNH2), a mixed 5-HT1B and 5-HT1D receptor agonist and saline (control) were alternately injected. Following the S-CM-GTNH2 treatment alone, animals exhibited an erratic running style, involving side-to-side movements of the head, without change in the overall accuracy of their locomotor trajectories, but with substantial decrease in their running speed. When distracting peripheral lights were introduced at the mid-points of the animals' run, in the weaker distracting condition (unilateral distractor) only, distraction indexes were found lower following the S-CM-GTNH2 treatment than following the other drug or saline treatments. It is concluded that serotonin, via 5-HT1B-1D receptors, may induce an elevation of the visual distractibility threshold by modulating directly the transmission of the primary visual signal.

Paratope characterization by structural modelling of two anti-cortisol single-chain variable fragments produced in E. coli.

Two monoclonal antibodies (mAbs), 5A4 and 6D6, directed against cortisol, have been obtained; 6D6 is used in an assay kit for cortisol. The antibodies also recognize other, structurally related steroids present in the sample assayed. To improve the specificity of the assay, we aimed to minimize the recognition of non-cortisol steroids by the two anti-cortisol mAbs. Our strategy consisted in constructing an efficient expression vector in E. coli which produced the single-chain variable fragment (scFv) of the mAbs in the periplasmic space. We demonstrated that temperature and inducer concentration of the bacterial culture influenced dramatically the yield of active scFv. From the nucleotide sequence we constructed a three-dimensional model of the two variable fragments in order to understand why related steroids are, or are not recognized by the antibody. For both antibodies, we have identified chemical groups which are probably involved in the binding of the steroid haptens and the antibodies. The hydrophobic pocket formed by the antibody comprises two or three tryptophan residues which can interact with the steroid nucleus by stacking. The serine at position 35 of the heavy chain is buried in the back of the pocket and can form a hydrogen bond with the 20-keto group of the cortisol. The stacking interactions and the hydrogen bond orient the steroid in the pocket. This reactivity of the binding site is sustained by the analysis of the cross-reactions of related steroids with the mAbs.

Effects of dorsal rhizotomy and selective lesion of serotonergic and noradrenergic systems on 5-HT1A, 5-HT1B, and 5-HT3 receptors in the rat spinal cord.

Autoradiographic studies were performed in combination with dorsal rhizotomy or selective lesion of descending serotonergic or noradrenergic systems in an attempt to identify the neuronal cell types endowed with the serotonin 5-HT1A, 5-HT1B and 5-HT3 receptors in the rat spinal cord. Unilateral sectioning of seven dorsal roots (C4-T2) at the cervical level produced a marked decrease (approximately-75%, 10 days after the surgery) in the binding of [125I]iodozacopride to 5-HT3 receptors in the superficial layers of the ipsilateral dorsal horn, further confirming the preferential location of these receptors on primary afferent fibres. In addition, a significant decrease (approximately 20%) in the binding of [3H]8-OH-DPAT to 5-HT1A receptors and of [125I]GTI to 5-HT1B receptors was also observed in the same spinal area in rhizotomized rats, suggesting that a small proportion of these receptors are also located on primary afferent fibres. The labelling of 5-HT1B receptors was significantly decreased (-12%) in the dorsal horn at the cervical (but not the lumbar) level, and that of 5-HT3 receptors was unchanged in the whole spinal cord in rats whose descending serotonergic projections had been destroyed by 5,7-dihydroxytryptamine. Conversely, the labelling of 5-HT1A receptors was significantly increased in the cervical (+13%) and lumbar (+42%) dorsal horn in 5,7-dihydroxytryptamine-lesioned rats. Similarly, [3H]8-OH-DPAT binding to 5-HT1A receptors significantly increased (+26%) in the lumbar (but not the cervical) dorsal horn in rats whose noradrenergic systems had been lesioned by DSP-4. The labelling of 5-HT1B receptors was also increased (+31% at the cervical level; +17% at the lumbar level), whereas that of 5-HT3 receptors remained unchanged in these animals. These data indicate that complex adaptive changes in the expression of 5-HT1A and 5-HT1B receptors occurred in the rat spinal cord following the lesion of descending monoaminergic systems.

Biochemical and pharmacological characterization of serotonin-O-carboxymethylglycyl[125I]iodotyrosinamide, a new radioiodinated probe for 5-HT1B and 5-HT1D binding sites.

There is a lack of radioactive probes, particularly radioiodinated probes, for the direct labeling of serotonin-1B (5-HT1B) and serotonin-1D (5-HT1D) binding sites. Serotonin-O-carboxymethylglycyltyrosinamide (S-CM-GTNH2) was shown previously to be specific for these two subtypes; we, therefore, linked a 125I to its tyrosine residue. Biochemical and pharmacological properties of S-CM-G[125I]TNH2-binding sites were studied by quantitative autoradiography on rat and guinea pig brain sections. S-CM-G[125I]TNH2 binding is saturable and reversible with a KD value of 1.3 nM in the rat and 6.4 nM in the guinea pig. Binding is heterogeneous, paralleling the anatomical distribution of 5-HT1B sites in the rat and of 5-HT1D sites in the guinea pig. The binding of 0.02 nM S-CM-G[125I]TNH2 was inhibited by low concentrations of 5-HT, S-CM-GTNH2, CGS 12066 B, 5-methoxytryptamine, and tryptamine in both species. Propranolol inhibited the radioligand binding with a greater affinity in the rat than in the guinea pig. Conversely, 8-hydroxy-2-(di-n-propylamino)tetralin inhibited S-CM-G[125I]TNH2 binding with a greater affinity in the guinea pig than in the rat. Other competitors, specific for 5-HT1C, 5-HT2, 5-HT3, and adrenergic receptors, inhibited S-CM-G[125I]TNH2 binding in rat and guinea pig substantia nigra and in other labeled structures known to contain these receptors, but only at high concentrations. S-CM-G[125I]TNH2 is then a useful new probe for the direct study of 5-HT1B and 5-HT1D binding sites.

Traps in displaying optical performances of a progressive-addition lens.

Typical traps when displaying the partial optical performances of a progressive-addition lens (PAL) are presented. The PAL is briefly described first. Then the ray-tracing software is described in detail. It permits the computation of the optical performance of the PAL in typical cases. For a reference PAL optical partial performances, which are computed in different cases, are displayed. The plots show that the performance depends on the computation conditions, that displaying only some areas of the partial performance may lead to traps for the characterization of the PAL, and that coma must be taken into account to obtain a precise measurement.

Pharmacological characterization of serotonin-O-carboxymethyl-glycyl-tyrosinamide, a new selective indolic ligand for 5-hydroxytryptamine (5-HT)1B and 5-HT1D binding sites.

The affinity of a new serotonin (S) derivative, serotonin-O-carboxymethyl-glycyl-tyrosinamide (S-CM-GTNH2), for the various 5-hydroxytryptamine (5-HT)1 receptor subtypes was tested using quantitative autoradiography on rat and guinea pig brain sections. In the rat, S-CM-GTNH2 is 57 and 24 times more potent at 5-HT1B sites (IC50 = 28 nM) than at 5-HT1A (IC50 = 1600 nM) and 5-HT1C sites (IC50 = 670 nM), respectively. In the guinea pig, the affinity of S-CM-GTNH2 for 5-HT1D sites (IC50 = 67 nM) is 21 times higher than at 5-HT1A sites (IC50 = 1400 nM). S-CM-GTNH2 shows a low affinity (less than 10 microM) for 5-HT2 and 5-HT3 binding sites. This new ligand is therefore highly specific for 5-HT1B and 5-HT1D binding sites and can be used to further characterize the involvement of these subtypes in physiological studies focusing particularly on behavioral effects.

Rapid and specific enzyme immunoassay of serotonin.

A new, highly sensitive enzyme immunoassay (EIA) of serotonin (5HT) is described. The assay is based on the competition between N-succinyl-glycinamide-serotonin (N-SGA-5HT, obtained by acylation of the 5HT in the sample to be assayed) and an enzymic tracer, N-succinyl-5HT-acetylcholinesterase, for binding to rabbit polyclonal antibody coated onto the wells of microtiter plates. The antibody is directed against an immunogen obtained by coupling N-succinyl-5HT to glycyl-bovine serum albumin. The EIA permits the accurate measurement of as little serotonin as 0.5 nmol/L (1.8 pg per well) in blood, plasma, serum, cerebrospinal fluid, urine, platelets, and other tissues, with no significant cross-reactivity with other compounds. The results obtained correlate well with those obtained by HPLC after extraction. The assay has the advantage of permitting the measurement of 5HT in up to 500 samples in as little as 3 h.

A new 5-hydroxy-indole derivative with preferential affinity for 5-HT1B binding sites.

The affinities of several 5-hydroxy-indole derivatives for serotonin-1 (5-HT1) binding site subtypes, labeled with 2 nM [3H]5-HT, were assessed by quantitative autoradiography on rat brain sections. The results obtained with known ligands, namely 5-hydroxytryptamine (5-HT), 5-methoxytryptamine (5-Me-OT), 5-methoxy-N,N- dimethyl-tryptamine (5-Me-ODMT), 5-hydroxy-N,N-dimethyl-tryptamine (bufotenine) and 8-hydroxy-2-[di-N-propylamino]tetralin (8-OH-DPAT) demonstrate the reliability and the advantages of this technique for pharmacological studies. Novel serotonin derivatives were synthesized by carboxymethylation of the hydroxyl group. One of those new ligands, serotonin-O-carboxy-methyl- glycyl-tyrosinamide (S-CM-GTNH2), inhibited 2 nM [3H]5-HT binding to the substantia nigra with an IC50 of 22.4 nM, a value which is 22 times lower than that found in the dentate gyrus and choroid plexus. This demonstrates the preferential affinity of S-CM-GTNH2 for 5-HT1B versus 5-HT1A and 5-HT1C binding sites. S-CM-GTNH2 contains a tyrosine residue, which may be useful for the synthesis of a radioactive iodinated molecule and for the preparation of 'long-lasting ligands' linked through peptide bonds with a protein. These derivatives could be of great interest for ultrastructural and behavioral studies relevant to 5-HT1B sites.