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The ex vivo identification of dopaminergic metabolites present in rat striata after (L-DOPA + benserazide) treatment is reported. The different metabolites have been identified as the trimethylsilyl derivatives in the striatal extracts by gas chromatography/mass spectrometry.

International audience; This work was carried out to evaluate the potential in vivo toxicity of 3,4‐dihydroxyphenylacetaldehyde (DOPAL), an aldehyde formed from dopamine by monoamine oxidase (MAO) that is oxidised mainly to 3,4‐dihydroxyphenylacetic acid (DOPAC) by brain aldehyde dehydrogenases (ALDH). In this study, male Sprague‐Dawley rats were treated with levodopa (L‐dopa)‐benserazide, which increases DOPAL production by MAO, and disulfiram, an irreversible inhibitor of ALDH, which reduces the formation of DOPAC from DOPAL. An acute systemic intraperitoneal (i.p.) injection of 100 mg/kg disulfiram and L‐dopa‐benserazide (100 mg/kg + 25 mg/kg, 24 hr later) significantly increased DOPAL striatal level. A 30‐day treatment with disulfiram (100 mg/kg i.p., once every 2 days) and L‐dopa‐benserazide (100 mg/kg + 25 mg/kg, two times/day) did not affect either indexes used to assess integrity of the nigrostriatal dopaminergic neurones (i.e., the striatal content in dopamine and binding to the vesicular monoamine transporter on striatal membranes). These results do not evidence any deleterious effect of DOPAL and argue against toxicity of L‐dopa therapy

Uptake blockers and substrates are likely to recognise a common binding domain on the dopamine neuronal transporter (DAT). Among cations that form ionic gradients at the level of the cellular plasma membrane, Na + is the only one that can stimulate their binding. The binding stimulation appears over Na + concentrations ranging from 0 to 10–60 mM; at higher Na + concentrations, binding reaches a plateau or decreases, according to the uptake blocker that is studied. The majority of the other cations, including K + , Ca 2+ , Mg 2+ and Tris + , inhibit the binding of uptake blockers. Several metals impair binding to the DAT and/or the dopamine transport, but, under specific conditions, some of them, and chiefly Zn 2+ , stimulate binding. The complex relationships between cations, uptake blockers and the DAT suggest that cations recognise at least three different sites: the first one, site 1, is for cation-induced binding inhibition; the second one, site 2, is for Na + -induced binding stimulation; and the third one, site 3, is for Zn 2+ -induced binding stimulation. Modelling of the interactions between Na + , K + and radioligands allows a better understanding of the effects of cations at sites 1 and 2, and of uptake blockers at site 1. Some anions also facilitate the binding of uptake blockers to the DAT, as far as they are associated with Na + . The dependence of the binding of dopamine on ions could be involved in its preferential inward transport and used by uptake blockers for their own binding to the DAT.

The reaction of 6-methyl-5,6-dihydroisoindolo[2,1-a]quinazolin-5-one with maleinimides in the ratio 1:2 was investigated. The products of the reaction were tricyclic derivatives of 7-azabenzonorbornene system 2-methyl-20-R-11-(1-R-2,5-dioxotetrahydro-1H-3-pyrrolyl)-2,10,20-triazahexacyclo[9.6.5.01,10.04,9.012,17.018,22]docosa-4(9),5,7,12,14,16-hexaene-3,19,21-trione. Their structure was established by the X-ray analysis, and a probable mechanism of the reaction is considered.

We have compared the effects of an i.p. pretreatment with L-DOPA (200 mg/kg) associated with benserazide (25 mg/kg) on neurotoxic effects of either 6-hydroxydopamine (6-OHDA) (50 microg, 10 microl per mouse) or 1-methyl-4-phenylpyridinium (MPP+) (17.5 microg, 10 microl per mouse). The striatal dopamine (DA) content, the vesicular monoamine transporter (VMAT2) density, as well as the hypothalamic norepinephrine (NE) content were measured 8 days after treatments. The L-DOPA-benserazide pretreatment worsened by 65% the 6-OHDA-induced depletion in striatal DA. On the contrary, it reduced by 42% the MPP+-induced depletion in striatal DA and by 54% the MPP+-induced decrease in VMAT2 density. It was noticed that the L-DOPA-benserazide pretreatment did not modify the marked decrease in hypothalamic NE content induced by 6-OHDA.

At 20 degrees C, [3H]GBR 12783, {1-[2-(diphenylmethoxy)ethyl]4-(3-phenyl-2-([1-3H]propenyl)-pip era zine} dissociated from the dopamine neuronal carrier present in rat striatal membranes with a t1/2 value of 27 min. At this temperature, KCI, CaCl2 and MgCl2 increased the binding dissociation, revealing that they recognize a binding site which is not mutually exclusive with that of [3H]GBR 12783. The comparison of the ability of KCl to increase the binding dissociation (by 160% at 30 mM KCl) with its potency as a binding inhibitor (Ki-2.6 +/- 0.3 mM) suggests an involvement of two recognition sites for K+ in binding inhibition, a not mutually exclusive site and another, mutually exclusive, site. Divalent cations mainly inhibited the binding via a mutually exclusive site since 3 mM Ca2+ and 10 mM Mg2+ increased the binding dissociation by 90% at 20 degrees C whereas their Ki values were 0.049 +/- 0.006 and 0.141 +/- 0.035 mM, respectively. Involvement of this mutually exclusive site was also supported by the persistence of the binding inhibition elicited by Ca2+ and Mg2+ at 0 degree C, a temperature at which they reduced the binding dissociation. At 20 degrees C, 100 mM NaCl did not modify [3H]GBR 12783 binding but it antagonized the binding dissociation elicited by inhibitory cations. Ca2+ reduced the off-rate of [3H]GBR 12783 binding at 0 degree C and in the presence of 100 mM Na+. Finally, [3H]GBR 12783-binding dissociation was increased by high 'cytosolic' K+ while 'synaptic' concentrations of Na+, K+, Ca2+, Mg2+ and Cl- were ineffective. A reduction of H2PO4-/HCO3- from 10 to 5 mM and a substitution of 5 mM H2PO4-/HCO3- by 5 mM Cl- increased the binding dissociation, suggesting that an anion-binding site could also regulate the binding.

We have considered the in vivo striatal binding of two ligands of the neuronal dopamine uptake complex: [ 3 H]cocaine and [ 3 H]mazindol. The [ 3 H]cocaine tracer dose labelled the dopamine uptake complex in striatum but not the noradrenaline complex in cerebellum. On the contrary, the [ 3 H]mazindol tracer dose induced a marked labelling of the noradrenaline uptake complex in cerebellum; its prevention by desipramine (5 mg/kg) increased simultaneously the cerebral bioavailability and thereby the striatal labelling of the dopamine transporter. In mice submitted to treatments modifying dopaminergic transmission either to decrease it (gammabutyrolactone, 750 mg/kg, i.p.) or to increase it ( l -DOPA, 200 mg/kg, i.p., dexamphetamine, 4 mg/kg, s.c., or their combination), only dexamphetamine pretreatment significantly reduced [ 3 H]cocaine and [3H]mazindol binding. Thus it appears that the level of dopamine transmission would not interfere with the in vivo quantification of striatal dopamine uptake sites assessed with either ligands.

We have studied the effect of various agents on the decreases in striatal levels of dopamine (DA) and its metabolites which were observed 14 days after an intracerebroventricular (i.c.v.) administration of 50 micrograms 6-hydroxydopamine (6-OHDA) to mice. A pretreatment of mice with either a tyrosine hydroxylase inhibitor (alpha-methyl-p-tyrosine), a D2 receptor agonist (bromocriptine) or antagonist (haloperidol), or a vesicular uptake inhibitor (tetrabenazine) did not modify the 6-OHDA-induced decreases in DA and metabolites, indicating that DA synthesis, vesicular storage and neuronal firing rates are not mainly involved in the 6-OHDA-induced toxicity on the DA neurons. Conversely, a pretreatment with L-DOPA + benserazide potentiated the 6-OHDA-induced decreases in striatal levels of DA, homovanillic acid and 3-methoxy-tyramine. This effect was not due to an increased 6-OHDA uptake via the neuronal carrier since a pretreatment with L-DOPA + benserazide, performed 1-1.5 h before sacrifice, decreased the apparent affinity of the uptake, an effect which disappeared when considering the total DA concentration present in incubation medium ([3H]DA and cold released DA). In conclusion, potentiation of the 6-OHDA neurotoxicity by L-DOPA rises again the important problem of the safety of the latter drug in therapeutics.

6-Fluoro-serotonin (6F-5-HT) was previously identified in the rat brain after peripheral administration of 6-fluoro-DL-tryptophan, a serotonin (5-HT) synthesis inhibitor. These present studies, performed with rat brain synaptosomes show that: i-neuronal 6F-5-HT uptake partly involved the 5-HT transporter since it was inhibited by clomipramine, a 5-HT uptake inhibitor, ii-6F-5-HT blocked the synaptosomal uptake of 3H-5-HT, with an IC50 value of 98 +/- 13 nM, and iii- 6F-5-HT induced 3H-5-HT release from preloaded synaptosomes, with an EC50 value of 95 +/- 6 nM; this release was decreased in the presence of clomipramine, suggesting the involvement of the 5-HT transporter. This release was also reduced when using synaptosomes from reserpinized rats, suggesting that the vesicular pool also participates to the 3H-5-HT release induced by 6F-5-HT. So, 6F-5-HT behaved as a substrate for the 5-HT neuronal transporter.

Some features of the band structure of GaSb have led to a renewed interest in this material. It is well known that Ga(Al)Sb alloys are good candidates to realize avalanche photodetectors, due to their high hole kp/electron kn ionization coefficient ratio. In addition, recent studies have shown GaSb to be attractive for realizing tunneling barriers exhibiting a high value of the peak-to-valley current ratio or IR photodectectors. In order to optimize such devices, the passivation of GaSb is of great interest. Unfortunately, very few investigations have been reported in the literature on GaSb passivation. This paper reports experimental results concerning GaSb surface passivation using a chemical sulfuration method. Physicochemical analysis is attempted through ellipsometric, photoluminescence, and Auger electron spectroscopy measurements. Polluting oxygen and carbon agents are found to be removed from the surface using this process, leading to Schottky diodes of better quality. In addition, the sulfur treatment is shown to stabilize the cleaned surface.

Chronic developmental lead (Pb) exposure has long been associated with cognitive dysfunction in children and animals. N-methyl-D-aspartate (NMDA) receptors, important in the synaptic mechanisms involved in learning and memory, are key target of lead toxicity. D-cycloserine (DCS), a partial agonist of the NMDA associated glycine site, has been recognised as a potential cognitive enhancer. We investigated the potential effects of Pb exposure (lead acetate 0.2% through the drinking water) during gestation and lactation (GL), on the spatial learning and memory capacities of PN32 rats. We also evaluate the ability of DCS (30 mg/ml), administered daily 24h after weaning during 15 days, to attenuate Pb neurotoxicity-induced cognitive deficits. Results indicate that rats exposed to lead during gestation and lactation have a significantly increased latency to find the hidden platform and cover a significant longer distance compared to control-vehicle in the learning phase of the Morris water maze. However, the administration of DCS to GL animals improved significantly their learning performances compared with GL-vehicle. In contrast, there is no significant difference between all groups during the probe test and the visual cue test. In conclusion, DCS enhancement of the NMDA receptor function is an effective strategy to ameliorate neurotoxicity lead-associated spatial learning deficits. Keywords: Neurotoxicity; Lead; Development; D-Cycloserine; Learning; Rat. Des etudes faites chez l’homme et l’animal montrent qu’une exposition chronique au plomb durant le developpement provoque des alterations des fonctions cognitives. Les recepteurs au glutamate de type Nmethyl-D-aspartate (NMDA), importants dans les mecanismes synaptiques impliques dans l’apprentissage et la memoire, sont les principales cibles du plomb. Il a ete montre que le D-cycloserine, un agoniste partiel du site glycine associe aux recepteurs NMDA, peut ameliorer les fonctions cognitives. Nous avons etudie les effets possibles d’une exposition au plomb (acetate de plomb 0.2% dans l’eau de boisson) pendant la gestation et la lactation (GL), sur les performances d’apprentissage spatial et de memorisation chez des rats âges de 32 jours. Nous avons egalement evalue la capacite du D-cycloserine (30 mg/ml), administre quotidiennement 24h apres le sevrage durant 15 jours, a attenuer les deficits cognitifs induits par le plomb. Nos resultats indiquent que les rats exposes au plomb pendant la gestation et la lactation mettent signicativement plus de temps et parcourent une plus grande distance que les animaux controle pour trouver la plateforme immergee au cours de la phase d’apprentissage de la piscine de Morris. Toutefois, l’administration de DCS aux animaux GL ameliore significativement leurs performances d’apprentissage comparees a celles des animaux GL non traites au DCS. Aucune difference de motivation ou des capacites de guidage visuo-moteur ne sont presents chez les GL. Donc, l’amelioration de la fonction des recepteurs NMDA pourrait etre une strategie efficace pour ameliorer les deficits d’apprentissage spatial associes a la neurotoxicite au plomb. Mots cles: Neurotoxicite; Plomb; Developpement; D-Cycloserine; Apprentissage; Rat.

Photon emission in the wavelength intervals 17-24 AA and 100-200 AA following single and double electron capture in collisions of O6++H2 at 3.8 keV amu-1 has been analysed. The overall single electron capture features on both ion cores are similar and show dominant population of n=4 on O6+(1s2)1S0 and O6+(1s2s)3S1. At variance to the capture from He, double 'correlated' capture on O6+(1s2)1S0 appears as a minor channel.

Single and double electron transfer from He into the ground state ion O6+(1s2)1S0 and the metastable ion O6+(1s2s)3S1 have been studied in collisions at v=0.39 v0. The single capture takes place dominantly into the n=3 shell for both ions; for O6+(1s2s)3S1 the transfer excitation ending in O5+(1s2p3l) represents of the order of 10% of the core conserving capture. The single capture main features are similar for both ion configurations. The double capture into the ground state and the metastable ion is discussed, assuming that its main features (energy gain and thus binding energy) are also similar.

The specific binding of [3H]l-[2-(diphenyl-methoxy)ethyl]-4-(3-phenyl-2-propenyl)piperazine([3H]GBR 12783) to the dopamine (DA) neuronal carrier present in membranes prepared from rat striatum was not affected when Cl– was replaced by either Br– or NO3–. In media containing Cl–, Br–, or NO3–, d-amphetamine and DA competed with the radioligand in a monophasic manner with Hill coefficients of close to 1 (0.94–1.12). Replacement of CT by Br– impaired the ability of some substrates (d-amphetamine, DA, p-hydroxyamphetamine, and m-tyramine) to compete with [3H]GBR 12783. The potency of Br– to decrease the affinity of substrates for the specific binding site was significantly correlated (t = 7.07, p < 0.001) with their affinity for this binding site. These results suggest that the various substrates tested could bind to recognition sites in which Cl– is differently involved; as a consequence, substrates could bind to the neuronal carrier by means of partly different links. In experiments dealing with the specific uptake of [3H]DA, F–, NO3–, is-ethionate–, or acetate– was unable to substitute for Cl–, whereas Br– was quite a total substitute. Replacement of Cl– by equimolar concentrations of either NO3 or isethionate– resulted in inhibition curves of DA specific uptake with Hill coefficients of close to 1 (0.77 and 1.04, respectively); this indicates that both NO3– and isethionate” are devoid of inhibitory effects on neuronal uptake and are quite ineffective substitutes for Cl–. Kinetic analyses performed in different experimental conditions provide consistent results revealing that decreasing the CT concentration induced a raise in apparent Km of DA without modification of the Fmax. On the other hand, the apparent Km values of Cl– for the stimulation of the neuronal uptake of DA decreased when the DA concentration increased. These data are consistent with a co-transport of Cl– and DA by the neuronal uptake system, with CT being the driving force.

The chemistry and electronic properties of the Ag/GaSb (110) interface formed at room and low temperature have been recently studied with a number of surface analysis techniques. All the results agree to show that at low temperature and at low coverage, the Ag layer is two dimensional and presumably composed of isolated atoms or very small 2D clusters, while three dimensional nucleation prevails at low temperature and higher coverage or at room temperature. Using quantitative Auger electron spectroscopy our study confirms the 2D growth at low temperature. It shows that the 3D evolution is not due to a simultaneous monolayer growth mechanism but agree with the enlargement of clusters whose area linearly increases with the number of impinging Ag atoms.

The first stages of the interface formed between Ag and cleaved (110) surfaces of GaSb are investigated at room (RT) and low temperature (LT≤140 K) by using the method of the vibrating capacitor. Surface photovoltage measurements are used to get informations about band bending and affinity variations. Ag depositions are made in the 10−4–1 A range. The results are in good agreement with those obtained in the 10−2–1 A range common to our results and ultraviolet photoemission spectroscopy (UPS) measurements. We discuss here more particularly LT results and set up different state distributions which could explain the experimental curves. Our analysis suggests that at the very beginning of the Ag deposition two successive acceptor–donor pairs are formed, followed by a more intricate system of states before reaching the monolayer. The reduction in clustering observed at LT by other methods has been a key to interpret the formation of these states. Eventually we propose a model to explain the evolution of the st...

Absolute X-ray and VUV emission cross sections have been measured for collisions of H-like C5+ and N6+ ions with H2 and He in the 0.18 au< nu

In mice, low doses (1-2-4 mg/kg s.c.) of dexamphetamine stimulated locomotor activity in a dose-dependent manner. Over the same range of doses the drug dose dependently inhibited the in vivo striatal binding of the dopamine uptake inhibitor, [ 3 H]GBR 12783. At 3 mg/kg dexamphetamine, the stimulant effect and the inhibition of the striatal binding of [ 3 H]GBR 12783 displayed a similar time course. Pretreatments that either increased (L-DOPA 200 mg/kg, benserazide 50 mg/kg i.p.) or decreased (reserpine 5 mg/kg s.c., α-methyl-p-tyrosine 200 mg/kg) striatal dopamine levels did not modify the inhibition by dexamphetamine of [ 3 H]GBR 12783 binding in vivo. This suggests that the inhibition is due to a direct effect of dexamphetamine, not mediated by endogenous dopamine, and further that a unique site is responsible for the neuronal uptake of dexamphetamine and for the binding of pure dopamine uptake inhibitors.

International audience; 3,4-Dihydroxyphenylacetaldehyde (DOPAL) is formed by the oxidative deamination of dopamine (DA) catalyzed by monoamine oxidases (MAO); then, the aldehyde is oxidized to 3,4-dihydroxyphenylacetic acid (DOPAC) by aldehyde dehydrogenases (ALDH) or reduced to 3,4-dihydroxyphenylethanol (DOPET) by aldose/aldehyde reductases. The present work aimed at evaluating the in vitro toxicity of DOPAL on catecholaminergic neuroblastoma SH-SY5Y cells which accumulate DA. DOPAL synthesis was stimulated by incubating cells with DA and blocking DOPAL oxidation by disulfiram, an irreversible inhibitor of ALDH. As evidenced by MTT reduction assays, DA and disulfiram treatments produced cell losses which increased with time. 10(-2)M DA reduced by 40% cell viability after a 1h treatment, when its TC(50) (concentration reducing viability by 50%) value was 7.3 x 10(-5) M after a 24 h treatment. For the same treatment periods, TC(50) values for disulfiram were 8 x 10(-5) and 8.7 x 10 (-7) M, respectively. MTT reduction assay performed after a 24h treatment followed by a 24h incubation in a drug-free medium evidenced that the toxicity of 10(-4)M DA or 10(-6)M disulfiram was potentiated by the second drug. HPLC measurements showed that DOPAL was produced at the early stages of the treatment by DA and disulfiram. This was evidenced by the significant increase in the ((DOPAL + DOPET)/DOPAC ratio observed after a combined 3h treatment by 10(-4)M DA and 10(-6)M disulfiram. Total contents in DA and DOPAL were greatly reduced at the end of a 15 h treatment, and disulfiram did not significantly enhanced the (DOPAL + DOPET)/DOPAC ratio. For both treatment durations, DOPAL and DOPET were detectable only in the extracellular medium. So, these results suggest that an early production of DOPAL could produce delayed toxic effects on SH-SY5Y cells. Production of DOPET and release of DOPAL could be important means for reducing DOPAL concentrations in dopaminergic neurons.

The ionic dependence of the [3H]-dopamine uptake was studied in transfected cells expressing the human neuronal transporter for dopamine (hDAT) or noradrenaline (hNET), and chimeric transporters resulting from the symmetrical exchange of the region from the NH2 terminal through the first two transmembrane domains (cassette I). Chimera A is formed by hDAT comprising cassette I from hNET, whereas chimera B corresponds to the reverse construct. The appearance or the intensity of a Cl(-)-independent component of transport was linked to the presence of the COOH terminal part of hNET in both monoclonal and polyclonal Ltk(-) cells (Cl(-) substituted by isethionate and NO3(-), respectively), and in transiently transfected COS-7 cells. Cassette I was also involved in the Cl(-)-dependence because the transport activity of polyclonal Ltk(-) cells expressing A was partly Cl(-)-independent and because Ltk(-) cells expressing transporters containing cassette I of hDAT displayed higher K(mCl)- values than cells expressing the reverse constructs. In monoclonal Ltk(-) cell lines, K(mNa)+ values and biphasic vs monophasic dependence upon Na(+) concentrations differentiate transporters containing cassette I of hNET from those containing cassette I of hDAT. In COS-7 cells, the exchange of cassette I produced a significant change in Hill number values. In Na(+)-dependence studies, exchange of the COOH terminal part significantly modified Hill number values in both Ltk(-) and COS-7 cells. Hill number values close to two were found for hNET and hDAT when sucrose was used as substitute for NaCl. The NH2 terminal part of the transporters bears some of the differences in the Na(+) and Cl(-)-dependence of the uptake that are observed between hDAT and hNET. Present results also support a role of the COOH terminal part in the ionic dependence.

1. In vitro, the ability of DEEP-NCS {1-[2-(diphenylmethoxy)ethyl]-4-[2-(4-isothiocyanatophenyl)ethyl]- piperazine} to inhibit [3H]-dopamine uptake by rat striatal synaptosomes was concentration-dependent and inversely related to the protein concentration. This inhibition was irreversible and resulted from changes in Vmax and KM. DEEP-NCS was less potent on noradrenaline, serotonin and choline transport. 2. One day after intrastriatal injections of DEEP-NCS (100 and 1000 pmol) in 20% dimethylsulphoxide, moderate decreases in the ex vivo dopamine uptake were observed in synaptosomes obtained from striatum injected with DEEP-NCS or solvent, and the contralateral uninjected striatum. 3. In similar conditions, 300 pmol DEEP-NCS in 45% 2 hydroxypropyl-gamma-cyclodextrin - 0.5% dimethylsulphoxide solution sub-totally reduced ex vivo dopamine uptake and mazindol binding, and moderately decreased choline and serotonin transport. These reductions were specific to DEEP-NCS-injected striata. A clomipramine pretreatment (16 mg kg-1 i.p. 1 h before) was performed in following experiments, since it reduced the DEEP-NCS-elicited decrease in serotonin uptake without affecting other indices. 4. One day after intrastriatal injection, DEEP-NCS elicited similar dose-dependent decreases in ex vivo dopamine uptake and mazindol binding (ID50=6.9-8 ng striatum-1). Changes in KM and Vmax for ex vivo dopamine transport produced by DEEP-NCS disappeared according to similar time-courses. 5. The t(1/2) for transporter recovery was 6. 1 days. This value should correspond to its actual turnover rate in vivo, since no change in transporter mRNA level was observed in substantia nigra ipsilateral to 300 pmol DEEP-NCS-injected striatum. 6. The results indicate that DEEP-NCS behaves as a potent, quite selective, irreversible inhibitor of the DAT, in vitro and in vivo. Its use in vivo suggests that the physiological half-life of the rat striatal DAT is close to 6 days.

We compared the ability of various dopamine (DA) uptake inhibitors to displace the in vivo striatal [ 3 H]GBR 12783 (1-[2(diphenylmethoxy) ethyl)-4-(3-phenyl-1[ 3 H]-2-propenyl)-piperazine) binding with their stimulant effect on locomotor activity on mice. GBR 12783 (8 mg/kg), GBR 13069 (10 mg/kg), cocaine (20 mg/kg), mazindol (3 mg/kg) or pyrovalerone (2 mg/kg) stimulated locomotion as long as they occupied the DA uptake complex. In contrast, nomifensine (3 mg/kg) did not stimulate locomotion although it completed with [ 3 ]GBR 12783 for the occupancy of the DA uptake complex at a significant level (> 50%). Administered at their ED 50 doses, GBR 12783, BTCP (N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine, GBR 13069, amineptine and dexamphetamine significantly increased locomotor activity whereas the other inhibitors tested did not. The locomotor response elicited by GBR 12783 (10 mg/kg) was not decreased by desipramine (20 mg/kg) nor by oxaprotiline (10 mg/kg). The increase in locomotion elicited by GBR 12783 was positively correlated with the basal locomotor activity of the mice. The stimulant effect of GBR 12783 was potentiated by SKF 525A and by budipine. Additional pharmacological properties might conceal the relationship between the effects of some DA uptake inhibitors on locomotion, and on in vivo occupancy of DA uptake sites.

We have studied the effects of several cations on (1) the neuronal uptake of [3H]dopamine ([3H]DA) and (2) the specific binding of 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenyl-2-[1-3H]propenyl)piperazi ne ([3H]GBR 12783) to a site associated with the neuronal carrier of DA, in preparations obtained from rat striatum. When studied under the same experimental conditions, both the uptake of [3H]DA and the binding of [3H]GBR 12783 were similarly impaired by the gradual replacement of NaCl by sucrose. In both processes, no convenient substitute for Na+ was found. Furthermore, potential substitutes of Na+ acted as inhibitors of the uptake with a rank order of potency as follows: K+ = Li+ > or = Cs+ > or = Rb+ > choline+ > Tris+ > sucrose, which was somewhat different from that observed in binding studies, i.e., Cs+ > Rb+ > choline+ > or = K+ > Li+ > Tris+ > sucrose. In the presence of either 36 mM or 136 mM Na+, [3H]DA uptake was optimal with 2 mM Mg2+, 1 mM K+, or 1 mM Ca2+. In contrast, higher concentrations of divalent cations competitively blocked the uptake process. K+ concentrations > 50 mM impaired the specific binding, whereas in the millimolar range of concentrations, K+ noncompetitively inhibited the uptake. Decreasing the Na+ concentration increased the inhibitory effect of K+, Ca2+, and Mg2+ on the specific uptake. An increase in NaCl concentration from 0 to 120 mM elicited a significant decline in the affinity of some substrates for the [3H]GBR 12783 binding site. An uptake study performed using optimal experimental conditions defined in the present study revealed that decreasing Na+ concentration reduces the affinity of DA for the neuronal transport. We propose a hypothetical model for the neuronal transport of DA in which both Na+ and K+ membrane gradients are involved.

Various characteristics of the in vivo striatal binding of [3H]GBR 12783 (1-[2-(diphenylmethoxy)-ethyl]-4-(3-phenyl-1[3H]-2-propenyl)pipera zine), a specific ligand of the neuronal dopamine uptake complex, were determined in mice. Increasing doses of the ligand revealed the saturability of the binding at a single site with half-maximal saturation at a dose of approximately 7 mumol/kg and an apparent maximal number of binding sites (Bmax) of 12.8 pmol/mg protein in striatum. Specific binding was prevented by various dopamine uptake blockers, pyrovalerone, GBR 13069, GBR 12783, N-[1-2-benzo(b)thiophenyl)cyclohexyl] piperidine, cocaine, methylphenidate and was inhibited in a stereoselective manner by the enantiomers of nomifensine. Other drugs which are not dopamine uptake blockers either did not modify [3H]GBR 12783 binding (the diphenylbutylpiperazine derivative flupenthixol) or increased it (the diphenylpiperazine derivative flunarizine or the chemically unrelated compounds fenfluramine and SKF 525A). A close correlation was found between occupancy of the striatal [3H]GBR 12783 binding site and the stimulant locomotor effect of the drug. A similar specific striatal binding of [3H]GBR 12783 was evidenced in both NMRI and CD1 strains. It was concluded that [3H]GBR 12783 administered in vivo provides a measure of the density of dopamine uptake sites in mouse striatum.

The Cl− dependence of the binding of substrates of the dopamine (DA) neuronal carrier observed in 3H GBR 12783 binding experiments was correlated with the affinity of substrates for the uptake process. Cl− ions were also required for the specific uptake of DA and for the inhibition of uptake by substrates including octopamine whose binding was not modified by substitution of Cl− by Br ions. In both 3H GBR 12783 and 3H mazindol binding studies, raising the temperature of incubation markedly reduced the affinity of uptake blockers whereas there was little or no decrease in the potency of substrates to compete for the specific sites of binding. This result was consistent with the mild increase of the Km of DA for the neuronal uptake when the temperature was raised from 12.5 to 37°C. Calculation of thermodynamic constants showed that the binding of substrates is generally characterized by a mild decrease in enthalpy associated with an increase in entropy, whereas the binding of uptake inhibitors led to a decrease of both parameters. However, the different uptake blockers displayed various entropy changes. These results suggest that i) substrates and uptake blockers could bind on the neuronal carrier of DA by different ways, and ii) the binding of each substrate or uptake blocker requires specific bonds.

We have investigated the thermodynamic properties of the binding of substrates and uptake blockers to the specific sites labeled with a tritiated dopamine uptake inhibitor (i.e., 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenyl-2-propenyl)piperazine ([3H] GBR 12783) or [3H]mazindol) using striatal membrane preparations. Raising the incubation temperature from 0 degrees C to 25 degrees C or 37 degrees C resulted in an increase in the dissociation constant of both [3H]mazindol and [3H]GBR 12783 for their specific sites of binding present in membrane suspensions obtained from either rabbit or rat striatum. However, maximal concentrations of binding sites were not affected by temperature. At all tested temperatures, both substrates and carrier blockers competed with either [3H]mazindol or [3H]GBR 12783 in a monophasic fashion, with Hill coefficients close to unity. Raising the temperature induced little or no increase in inhibition constants (Ki) for substrates (Ki ratio 37/0 degrees C less than 2.5). This is consistent with the mild increase of the Michaelis constant of dopamine for the neuronal uptake system when the incubation temperature was raised from 12.5 to 37 degrees C (from 126 to 406 nM). In contrast, increasing the temperature resulted in a more important increase in the Ki of uptake inhibitors (33 greater than Ki ratio greater than 5). Thermodynamic calculations showed that the binding of substrates is generally characterized by a mild decrease in enthalpy (range, -2- -6 kcal/mol) associated with an increase in entropy, whereas binding of uptake inhibitors led to a decrease of both parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to extend the comparison of the initial stages of Schottky barrier formation to different surfaces of III–V semiconductors, we present here an investigation with low‐energy electron diffraction, Auger electron spectroscopy, and ultraviolet photoemission spectroscopy of In– and Ag–GaSb(100) interfaces at room temperature and after annealing. The initial GaSb surfaces exhibit a (3×2) structure. The low‐coverage growth of In and Ag is essentially two dimensional. It is followed by substantial islanding (In) especially after annealing. Band bending measurements show no significant movement of the Fermi level from its initial position near the valence band maximum.

The spectroscopy of emitted radiation following double electron capture by low-energy Ne8+ from He shows state-selective capture into the n=2, n'=3 and 4 energy levels. These levels appear to favour radiative decay, whereas double capture to n=3, n'>or=3 will stabilise mostly via autoionisation.

De-excitation of doubly excited N4+(1s2ln'l') ions produced in N5+(1s2s 3S) (3.4 keV amu-1)+He, H2 collisions has been studied in the 1-5 nm wavelength range. It is shown that the spectrum consists of lines mostly due to states produced by core-conserving capture processes except for an intense peak around 2.9 nm that could be due to electron capture with simultaneous 2s-2p core excitation. Moreover, many lines can be identified as originating from doublet states.

Absolute cross sections for electron capture into different nl states for Ne8+ to He and H2 collisions in the 0.2-0.4 au velocity range have been measured. It is found that selective electron capture into the n=4 shell is a dominant mechanism for Ne8++He collisions, whereas a population of the n=4, 5 shells is observed for Ne8++H2 collisions.

The complex Cd(pyridoxine)Cl2 crystallizes in space group P21/c with a = 9.279(2), b = 7.289(3), c = 17.845(6) A and s = 114.36(2) A . The crystal structure has been determined using four-circle diffractometer data recorded at 24°C and refined by full matrix least-squares calculations to R = 0.048. It consists of infinite chains Cd-bridge-Cd. The Cd atom, in an octahedral environment, is bound to three chlorine atoms and three oxygen atoms of the ligand. Two chlorine atoms make a double bridge between two equivalent cadmium atoms. The pyridoxine molecule acts as a bidentate ligand through two oxygen atoms and as a bridge between two equivalent atoms. Moreover, the Cd2+ influence on B6 vitamin 13C NMR spectra has been investigated in aqueous solution. At pH ∼ 7, the pyridoxine reacts with the metallic ion as a zwitterion to give a 1.1 chelate. These results are in perfect agreement with the radiocrystallographic study.

Recrystallization of bis(dibenzylideneacetone)palladium from various solvents affords novel binuclear palladium-dibenzylideneacetone complexes of composition Pd2(Dibenzylideneacetone)3(Solvent). These new complexes were identified by spectroscopic (IR, NMR, UV, and mass) and thermogravimetric analyses, together with a confirmative crystallographic structure determination. The CC bonds of a given dibenzylideneacetone ligand coordinate separately to two palladium atoms to yield a binuclear complex in which each palladium atom exhibits trigonal coordination. The Pd—Pd distance is 3.245 A. Ligand exchange reactions, oxidative addition reactions, and complex formation reactions with p- and o-quinones were investigated and found to yield a variety of new organopalladium complexes.

Increasing doses of apomorphine elicited polyphasic changes in locomotor activity in mice, consisting of: (i) hypokinesia with a peak effect at 25 micrograms/kg, which was not antagonized by various neuroleptics used at the highest doses not changing spontaneous locomotor activity, except for haloperidol; (ii) a relative restoration of locomotor activity at 75 micrograms/kg; this effect was antagonized by all the neuroleptics tested (except clozapine) and was hardly affected by domperidone and sulpiride; this apomorphine-induced effect was markedly increased 12 days after ICV 6-hydroxydopamine, (iii) a further hypokinetic effect with a peak effect at 150 micrograms/kg-1 (occurring simultaneously with hypothermia) which was antagonized by all the neuroleptics tested (including sulpiride at low doses) except levomepromazine and clozapine, and was again hardly affected by domperidone; this hypokinesia was reduced after prior (24 h) administration of 5 mg/kg apomorphine, (iv) finally another restoration of locomotor activity was observed at doses of apomorphine above 200 micrograms/kg.