14,672 research outputs found

    Brain dialysis and dopamine: does the extracellular concentration of dopamine reflect synaptic release?

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    We considered the drug-induced circling behaviour of rats monolaterally lesioned with kainic acid (KA) as a marker of the dopamine (DA) concentration in the synaptic space. D-Amphetamine produced a dose-related increase in the DA concentration of the dialysate from an intact striatum and a proportional number of ipsilateral circlings. Pargyline or L-dihydroxyphenylalanine (L-Dopa), alone or in combination with benserazide, increased the concentration of DA to a similar or even higher level than d-amphetamine, but failed to elicit a circling response. Apomorphine given after these drugs at the peak of DA accumulation always induced circling behaviour. The results suggest that released DA may undergo different inactivation processes before reaching the dialysis probe, and that these processes may be differentlly affected by drug treatments. Alternatively, it may be suggested that DA can be released into the synaptic space, in a functional manner, or into the interstitial fluid, from where it cannot reach the synaptic receptors. © 1990

    Neonatal hypothyroidism induces striatal dopaminergic dysfunction

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    Oral administration of the antithyroid drug methimazole (50 mg/kg per day) to rats during the last six days of pregnancy, and subsequent daily s.c. injection of methimazole (20-30 mg/kg) to their pups from birth to postnatal day 30 provoked hormonal and somatic alterations resembling (with all caution to any association between rodent and human data) those of congenital hypothyroidism. The steady-state concentrations of striatal dopamine were similar in hypothyroid and euthyroid, 32-day-old rats, while the levels of the dopamine metabolites 3,4-dihydroxyphenylacetic and homovanillic acids were markedly decreased in hypothyroidism. The results of this and our earlier study [Vaccari A. and Gessa G. L. (1989) Neurochem. Res. 14, 949-955] show that the maximal synaptosomal uptake of [3H]dopamine, an index for the density of nigrostriatal dopaminergic terminals, and the maximum number of membrane [3H]tyramine binding sites, reflecting the concentration of the vesicular transporter for dopamine, were decreased in the hypothyroid striatum. There was also a loss of those D1-type dopaminergic receptors claimed to be located on neurons intrinsic to the striatum, and, consequently, dopamine-stimulated, D1-regulated adenylate cyclase activity was depressed. It is suggested that individual dopaminergic nerve endings in the neonatal hypothyroid striatum must contain more dopamine, owing to some loss of pertinent innervation and, therefore, to the presence of less vesicular transport sites for dopamine. Hypothyroidism-related decreases in the maximum number of striatal D1- and, reportedly, D2-receptors, plus the impairment of D1-coupled second messenger activity, may play a role in the derangement of those neurobehavioural patterns where a dopaminergic regulation is putatively implied

    Robert Buchanan 1841-1901: an assessment of his career.

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    PhDRobert Buchanan was widely regarded during his lifetime as a poet of distinction, a capable and powerful novelist, and a critic of some perception, yet his name is now associated only with one regrettable episode, while those of lesser men and women continue to be remembered for work inferior to his. A man possessing large reserves of energy, and pressed to write for a living at an early age, he produced much work that deserves the oblivion it has found; but his early verse, expressing his profound compassion for the sufferings of the unfortunate in the simplest language, some of his ballads, and not a little of his later more vatic verse, is still worthy of study. As a novelist his work is provocative and readable, but too often descends to the level of the sentimental melodrama which earned him, for a while, a very good income from the stage. As a critic he was not profound, but was quick to detect and praise expression of his own sympathy for humanity that came to represent for him art's highest aspiration; Dickens, Browning and Whitman were his heroes, and for the last two he did sterling work in helping them to gain widespread recognition. As a polemist he rushed into several arenas, for some of which his talents were not especially suited; but he publicly supported C. S. Parnell and Oscar Wilde when few found the courage to do so. An interesting man of impressive variety and undoubted talent has found an undeserved neglect, and a full-scale critical biography of Robert Buchanan is long overdue

    Calcium receptor antagonists modify cocaine effects in the central nervous system differently

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    The effect of different calcium antagonists on cocaine-induced dopamine (DA) release in the striatum, as measured by brain microdialysis in freely moving rats, and on cocaine-induced motor stimulation was studied. While two dihydropyridine calcium antagonists, nimodipine (20 mg/kg) and isradipine (2.5 mg/kg), prevented cocaine-induced DA release and motor stimulation, the diphenylalkylamine-type calcium antagonist flunarizine (20 mg/kg) strongly potentiated both effects of cocaine. Moreover, two calcium antagonists, veraparnil (20 mg/kg) and diltiazem (20 mg/kg), were ineffective. The results indicate that various classes of calcium antagonists differ in their interaction with the effects of cocaine in the CNS and suggest that dihydropyridine calcium channel antagonists might be clinically useful for the treatment of cocaine abuse. © 1990
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