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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 47 (1986), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract Catecholamine turnover in brain areas innervated by dopaminergic neurons was examined 2, 6, and 12 days after bilateral, N-methyl-D-aspartate lesions confined to the rat medial prefrontal cortex. The lesion produced a significant regional increase in the concentration of 3,4-dihydroxyphenylethylamine (DA, dopamine) in both the medial prefrontal cortex and the ventral tegmental area. DA concentrations were increased in the nucleus accumbens on day 6 (128% of control), in the ventral tegmental area on day 2 (130% of control), and in the medial prefrontal cortex on days 2 (145% of control) and 6 (127% of control). The only significant changes in the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC) (197% of control), and in the ratio DOPAC/DA (163% of control) were found in the medial prefrontal cortex on day 6 post-lesion. All parameters had returned to control levels by day 12. DA depletion after the administration of α-methyl-p-tyrosine (AMPT) was not significantly different between excitotoxin-lesioned and sham animals on day 6 in all brain regions. Noradrenaline (NA) and 3,4-dihydroxyphenylethyleneglycol concentrations and their ratios, and the depletion of noradrenaline after AMPT were also determined, and the lesion resulted in a significant regional increase in NA in both the nucleus accumbens and the ventral tegmental area. An elevation of NA (147% of control) in the nucleus accumbens was found on day 12. Since the excitotoxin lesion destroys corticofugal efferents from medial prefrontal cortex to the nucleus accumbens, the anterior corpus striatum and the ventral tegmental area, our results provide no evidence for a role of these cortical projections in the regulation of subcortical DA metabolism. Corticofugal efferents from the medial prefrontal cortex do appear to exert a modulatory effect over NA stores of the nucleus accumbens.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 39 (1982), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The binding of [3H]spiperone to membranes of the nucleus accumbens of the rat brain was studied in vitro and found to be of high affinity, rapid, saturable, reversible and stereospecific. Dissociation and saturation experiments indicated the presence of two specific binding sites with apparent dissociation constants of 70 pM and 〉1 nM. Specific binding with 25 pM [3H]spiperone represented 〉90% of total binding and was displaced by dopaminergic agonists, neuroleptic drugs and ergot derivatives. The rank order of potency for the ergot derivatives was bromocryptine 〉 pergolide 〉 lergo-trile, and that for D-2 antagonists was domperidone 〉 sulpiride 〉 molindone 〉 metoclopramide. Noradrenergic, histaminergic and serotonergic components of the binding were not detected. [3H]Spiperone binds to high-affinity sites in homogenates of nucleus accumbens, which are likely to be D-2 receptors.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: High-affinity uptake of neurotransmitter substrates in synaptosome-containing homogenates and tissue concentrations of amino acids were examined in subcortical areas 5–6 days after bilateral N-methyl-D-aspartate lesions confined to rat medial prefrontal cortex. D-[3H]Aspartate (32% of control) and [3H]γ-aminobutyric acid ([3H]GABA) (60% of control) uptakes were significantly reduced in medial prefrontal cortex, whereas [3H]choline (110% of control) uptake was unchanged, suggesting the production of axon-sparing lesions. The uptake of D-[3H]aspartate (76% of control), but not of [3H]GABA or [3H]choline, was significantly reduced in nucleus accumbens, with no concomitant reduction in amino acid concentrations. When examined in serial coronal sections, reduced D-[3H]aspartate uptake was confined to the most anterior 500 μm of nucleus accumbens (67% of contralateral sample). No significant reductions of uptake or amino acid concentrations were observed in caudate putamen or ventral tegmental area. These results suggest a role for glutamate or aspartate as neurotransmitters in projections from medial prefrontal cortex to anterior nucleus accumbens. Medial prefrontal cortex may represent the major excitatory cortical input to the nucleus accumbens.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 39 (1982), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The binding of [3H]spiperone, a neuroleptic/dopamine receptor ligand, to membranes of the ventral tegmental area of the rat was studied in vitro and found to be rapid, saturable, reversible, and of high affinity. Specific binding was displaced by the dopaminergic agonists dopamine, apomorphine, and 2-amino-6,7-dihydroxytetralin, and stereospecifically by the neuroleptic drugs butaclamol and flupenthixol. Bromocryptine and other ergots displaced the binding, as did the D-2 antagonists domperidone, molindone, metoclopramide, and sulpiride. Noradrenergic, histaminergic, and serotonergic components of the binding were not detected in displacement studies with various agonists and antagonists. These data are consistent with the hypothesis that [3H]spiperone labels dopamine receptors in the ventral tegmental area that are not linked to adenylate cyclase and are therefore likely to be of the D-2 type.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 38 (1982), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The rat ventral tegmentum (containing somata and dendrites of mesolimbic dopaminergic neurones) contained 1.3 μmnol/g wet weight of glycine. Slices of ventral tegmentum accumulated exogenous [3H]glycine by an energy-, temperature- and sodium-dependent mechanism. The uptake was mediated by two different transport systems; one system with relatively low affinity for glycine (Km∼400 μm) and the other a higher affinity for glycine (Km∼ 10 μm). Small amino acid analogues of glycine inhibited the uptake process, the most potent being taurine and β-alanine (47% and 44% inhibition, respectively, at 1 mm). Release of exogenous [3H]glycine by elevated potassium and by protoveratrine A was calcium-dependent and tetrodotoxin-sensitive. Glycine (500 μm-2 mm) potentiated the protoveratrine A-induced release of exogenous [3H]dopamine from slices of ventral tegmentum; this potentiation was blocked by strychnine (10 μm). A convulsant dose of strychnine elevated the concentration of 3,4-dihydroxyphenylacetic acid in the ventral tegmentum. Glycine is likely to be a transmitter in the ventral tegmentum and to have a role regulating the activity of somatodendritic regions of mesolimbic dopaminergic neurones.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 34 (1980), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The rat ventral tegmentum (containing dendrites and somata of mesolimbic neurones) contained 1.3 μg/g of dopamine, which was reduced to 40% of the control level by reserpine. Slices of ventral tegmentum were able to accumulate and release (elevated potassium or protoveratrine A) exogenous [3H]dopamine. In parallel studies the uptake mechanism in ventral tegmentum was shown to be virtually identical to the nerve terminal uptake of [3H]dopamine by slices of nucleus accumbens. The release of [3H]dopamine was indistinguishable from that observed in substantia nigra, where there is substantial evidence for dendritic mechanisms. Basal adenylate cyclase activity was present, but dopamine-stimulated activity was not detected. A high GABA concentration (7.7 μmol/g) was present in ventral tegmentum, in conjunction with an uptake and a release mechanism for [3H]GABA. GABA and muscimol elicited a small, reproducible efflux of [3H]dopamine, but an interaction between dopamine and [3H]GABA efflux was not observed. The results are in accord with transmitter roles for dopamine and GABA in the somatoden-dritic area of mesolimbic dopaminergic neurons.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 61 (1993), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The characteristics of binding sites in rat cerebral cortical synaptic membranes labeled by 125I-ifenprodil, a noncompetitive NMDA receptor antagonist, are described. 125I-ifenprodil was synthesized using Na125I in the presence of chloramine-T and purified by paper chromatography. Binding of the 125I-ligand was optimal at pH 7.7 in 5 mM Tris · HCl buffer. Equilibrium binding of 125I-ifenprodil was displaced by spermine (1 mM) but not by ifenprodil or its analogue, SL 82.0715 (both 16.7 μM). Zn2+, Ca2+, and Mg2+ inhibited specific binding of 125I-ifenprodil in a concentration-dependent manner, with IC50 values of 0.11, 1.1, and 1.7 mM, respectively. The dissociation constant (KD) for unlabeled ifenprodil determined by saturation binding was 205 nM. Scatchard plots of saturation data appeared curvilinear but were best described by a single-binding-site model (Hill coefficient = 0.95), with a density of binding sites (Bmax) of 141 pmol/mg of protein. Binding of 125I-ifenprodil was inhibited by polyamines, with a rank potency order of spermine 〉 spermidine 〉 putrescine = 1,3-diaminopropane. The pattern of inhibition produced by spermidine was apparently competitive. Ifenprodil congeners also fully inhibited polyamine-sensitive binding of 125I-ifenprodil, with a rank potency order of ifenprodil 〉 SL 82.0715 = tibalosine 〉 nylidrin = isoxsuprine. It was found that σ/antitussive agents partially inhibited specific binding, but inclusion of the σ drug GBR 12909 had little effect on the binding of 125I-ifenprodil, suggesting this site was not involved. The binding site labeled by 125I-ifenprodil is polyamine sensitive, has a discrete pharmacological profile, and apparently is unrelated to the σ site.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 19 (1972), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— trans-4-aminocrotonic acid, dl-cis-aminocyclohexane-ltarboxylic acid and 4-aminotetrolic acid were found to be competitive inhibitors of GABA uptake in rat brain slices. These inhibitors are analogues of extended conformations of GABA, which indicates that these conformations are important in the initial binding of this inhibitory transmitter to its transport carrier.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 24 (1975), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Cis-4-aminocrotonic acid, an analogue of GABA in a folded conformation, appears not to act as a GABA analogue with respect to bicuculline-sensitive postsynaptic receptors, ‘high affinity’ GABA uptake and GABA: 2-oxoglutarate aminotransferase in the mammalian central nervous system. On the other hand, trans-4-aminocrotonic acid, an analogue of GABA in an extended conformation, acts as efficiently as GABA with respect to each of the above systems, indicating that extended rather than folded conformations of GABA are likely to be important in the interaction of GABA with the specific macromolecules concerned.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 19 (1972), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— The influence of the following acetylenic analogues of GABA on GABA-metabolizing enzymes was studied in vitro: 4-amino-, 4-morpholino-, 4-piperazino-, 4-piperidino- and 4-pyrrolidinotetrolic acid. 4-Aminotetrolic acid was a linear competitive inhibitor of GABA transaminase activity in extracts of rat cerebral mitochondria and a linear noncompetitive inhibitor of this enzyme activity in extracts of P. fluorescens when activity was measured with GABA as the variable substrate. From these results it was calculated that the dissociation constants for the binding of 4-aminotetrolic acid to the pyridoxal form of these enzymes are approx. 1 mM. The other substituted tetrolic acids did not influence either transaminase activity under the conditions studied. None of the substituted tetrolic acids influenced the L-glutamic acid decarboxylase activity in extracts of rat cerebral cortex and of E. coli.
    Type of Medium: Electronic Resource
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