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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 79 (1983), S. 115-119 
    ISSN: 1432-2072
    Keywords: Dopamine ; Acquisition ; Brain lesions ; 6-Hydroxydopamine ; Neonatal rat ; Operant behavior
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In an attempt to examine the ability of brain dopamine (DA) depletion to alter learning ability in the developing rat, the rate of acquisition of a positively reinforced lever pressing response was examined in rats during days 30–45 of life following treatment with desmethylimipramine (DMI, 20 mg/kg IP) and 6-hydroxydopamine (6-OHDA, 35 μg intraventricularly) at 3 and 6 days of age, respectively. The 6-OHDA treatment produced a 40%–70% reduction of brain DA without altering growth rate, water intake, or locomotor activity. On the average, water-deprived control rats achieved the criterion for acquisition (50 reinforced lever presses/h) on a fixed-ratio 1 schedule of water reinforcement after 3.1±0.5 sessions (mean ± SEM). In contrast, nearly one-fourth of the DMI + 6-OHDA-treated rats failed to acquire the response after 16 sessions and the remaining 6-OHDA-treated rats required more than twice as long as controls for acquisition (7.8±0.7 sessions). These results suggest that brain DA depletion in neonatal life can impair the acquisition of an operant response during development and that this deficit is independent of changes in growth rate or locomotor activity.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Adenosine ; Dopamine ; Antipsychotic ; Locomotion ; Ataxia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The adenosine agonists 5′-N-ethylcarboxamidea-denosine (NECA), 2-chloroadenosine (2-CLA), N6-cyclohexyladenosine (CHA), N6-cyclopentyladenosine (CPA), 2-(phenylamino)adenosine (CV-1808) and R and S isomers of N6-phenylisopropyladenosine (R-PIA and S-PIA) decreased spontaneous locomotor activity in mice and, except for CPA, did so at doses that did not impair motor coordination, a profile shared by dopamine antagonists. CV-1808, the only agent with higher affinity for A2 as compared with A1 adenosine receptors, displayed the largest separation between locomotor inhibitory and ataxic potency. Like dopamine antagonists, NECA and CV-1808 also decreased hyperactivity caused by d-amphetamine at doses that did not cause ataxia whereas A1-selective adenosine agonists reduced amphetamine's effects only at ataxic doses. Unlike dopamine antagonists, adenosine agonists inhibited apomorphine-induced cage climbing only at doses that caused ataxia. Involvement of central adenosine receptors in these effects was suggested by the significant correlation obtained between potency for locomotor inhibition after IP and ICV administration. Affinity for A1 but not A2 adenosine receptors was significantly correlated with potency for inducing ataxia. These results suggest that the behavioral profile of adenosine agonists in mice is related to their affinity for A1 and A2 adenosine receptors and indicate that adenosine agonists produce certain behavioral effects that are similar to those seen with dopamine antagonists.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 147 (1999), S. 104-107 
    ISSN: 1432-2072
    Keywords: Key words MPTP ; Levodopa ; Parkinson’s disease ; Memory ; Dopamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The ameliorative effects of levodopa (l-3,4-dihydroxy-phenylalanine) on the motor impairment in Parkinson’s disease patients is well established, but characterization of its effects on the associated cognitive deficits is still incomplete. Objective: The present study determined the effect of different doses of levodopa on performance on a test of working memory in MPTP-treated rhesus monkeys, an animal model of Parkinson’s disease. Methods: Four MPTP-treated monkeys and their age-matched controls with the same experimental history as the MPTP-treated monkeys were tested on a spatial delay response task. Each daily session consisted of five trials at each of seven randomly presented delays (0, 10, 20, 30, 40, 50 and 60 s). Training was continued for 5 days in each of five different conditions. In the first condition, control and MPTP-treated animals performed the task without levodopa. In the second condition, both groups were tested with a dose of 100 mg of levodopa. In the third and fourth conditions, in which the doses of levodopa were increased to 250 and 500 mg, respectively, only the MPTP-treated animals were tested. In the final condition, the MPTP-treated animals where retested without levodopa. Results: Significant improvement was observed at all doses tested (range 100–500 mg). Conclusions: Levodopa can ameliorate memory impairments in this parkinsonian model.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Thyrotropin Releasing Hormone (TRH) ; Biogenic Amines ; Catecholamines ; Norepinephrine ; Dopamine ; Serotonin ; Antidepressants ; Depression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Synthetic thyrotropin releasing hormone (TBH) was administered to albino rats in order to determine the effects of this drug on norepinephrine-H3 metabolism in the brain. With the possible exception of a slight enhancement of release, acute or chronic administration of TRH had little effect on the disposition and metabolism of norepinephrine-H3 in rat brain. In addition, no significant changes were found in brain levels of endogenous norepinephrine, serotonin or dopamine following the injection of TRH. Thus, little evidence was found to support a possible relationship between the reported clinical antidepressant activity of TRH and its effects on norepinephrine metabolism in brain.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 1153-1165 
    ISSN: 1434-193X
    Keywords: Carbohydrates ; Phospholipids ; Glycolipids ; Sphingosines ; Ceramides ; Ceramides-1-phosphates ; Glycosylation ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -For the design of a synthesis of target molecule 1 the retrosynthetic analysis yielded building blocks 2-5, of which ceramide 2-phosphite derivative 2 and aminoethyl phosphite derivative 5 are known. The generation of α-glucosaminyl (1→6)inositol building block 3 was based on pseudodisaccharide 6 which was selectively benzoylated at 6b-O and then selectively benzylated at 3b-O to give 3. The synthesis of tetramannosyl building block 4 started from known ortho ester derivative 8 which was transformed into versatile mannosyl donors 13 and 18 and into acceptor 22. Reaction of 13 with 22 gave α-disaccharide 23, deacetylation and then mannosylation with 18 gave trisaccharide 25; ensuing deacetylation and mannosylation with 13 gave tetrasaccharide 27; deallylation, acetylation, regioselective removal of the anomeric O-acetyl group and treatment with CCl3CN/DBU afforded 4. Glycosylation of 3 with donor 4 led to pseudohexasaccharide 31 in high yield. Replacement of the O-acyl groups by O-benzyl groups and then exchange of the menthyloxycarbonyl group by an O-acetyl group gave 36 which enabled regioselective attachment of 2 and 5. To this end, the 6e-O-silyl group was removed and then the aminoethyl phosphate residue was attached with reagent 5 to give 38 in high yield. 1a-O-Deacetylation and then reaction with 2 afforded 40 as fully protected 1 which was liberated in two steps; treatment with acid removed all acid labile protective groups and finally catalytic hydrogenation afforded the desired GPI anchor 1 which could be fully structurally assigned.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1434-193X
    Keywords: Carbohydrates ; Phospholipids ; Glycolipids ; Sphingosines ; Ceramides ; Ceramide-1-phosphates ; Inositols ; Glycophosphosphingolipids, synthesis ; Glycophosphoinositol anchors ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The readily available 2,3:4,5-di-O-cyclohexylidene-D-myo-inositol derivative 3 was converted into the 1-O-unprotected D-myo-inositol derivative 6. Reaction with the phosphite derivative 7 of 3-O-tert-butyldimethylsilyl-protected ceramide furnished the target molecule D-erythro-ceramide-1-phosphoinositol (1). Reaction of O-(3,4,6-tri-O-acetyl-2-azido-β-D-glucopyranosyl)trichloroacetimidate (20) with 3 gave exclusively α(1→6)-connected glycoside 21 which was converted into the 1α-O-unprotected derivative 24. Reaction with the D-erythro-azidophytosphingosine-derived ceramide-1-phosphite derivative 17 led, after oxidation and removal of the cyanoethyl group, to protected 2-azido-D-glucopyranosyl-α(1→6)-D-myo-inositol-1-phospho-ceramide (25) which could be fully deprotected in two steps to afford the target molecule, the ceramide derivative of 2-amino-2-deoxy-D-glucopyranosyl-α(1→6)-D-myo-inositol-1-phosphate (2).
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1434-193X
    Keywords: Carbohydrates ; Phospholipids ; Glycolipids ; Diacylglycerolphosphates ; Glycophosphoinositol anchors ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The exploration of the molecular and structural basis for the sorting of GPI-anchored proteins is based on labeled partial structures of GPI′s which can be incorporated into the GPI anchor biosynthesis and cellular transport systems. To this end, from mannosyl donor 6 and the D-glucosaminyl-(1→6)-D-myo-inositol derivative 7 as acceptor, the pseudotrisaccharide 8 was prepared. Compound 8 was transformed into the GPI partial structures 5a,b which contain the pseudotrisaccharide ligated to two different phosphatidyl residues. Compounds 5a,b have Boc protection at the 2-amino group of the glucosamine residue (2b-position) and a free amino group at the 6b-position. The 6b-amino group was used for the ligation of the 3-(7-nitrobenzofurazan-4-yl)-aminopropanoyl group as a fluorescent label, the 5-azido-2-nitrobenzoyl and 4-azidophenylaminothiocarbonyl groups as photolabels, and the 4-azido-2-hydroxybenzoyl group as a radiolabel after the introduction of radioactive iodine by an electrophilic aromatic substitution. Thus, after acid-catalyzed removal of the protective groups, the unprotected target molecules 1-4 were obtained.
    Type of Medium: Electronic Resource
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