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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— Thiamylal, methohexital, secobarbital, amobarbital, pentobarbital, phenobarbital and barbital, and also chloral hydrate inhibited K-stimuiated acetylcholine (ACh) release from rat midbrain slices in a dose related manner. The concentrations required for 50% inhibition were related to the lipid partition coefficient. None of the barbiturates nor chloral hydrate inhibited unstimulated ACh release. Ethanol, chlordiazepoxide and 11-OH-Δ9-tetrahydrocannabinol were without effect on both unstimulated and stimulated ACh release. The results are discussed in terms of other effects of these drugs on the cholinergic system.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 26 (1976), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: —A superfusion system has been used to examine the effects of choline and the utilization of [3H]choline during resting and potassium-stimulated release of ACh from rat cerebrum slices. The rate of ACh release from unstimulated tissue, 0·25 nmol/g per min, increased 8-fold when the concentration of KCl in the superfusing medium was increased from 5 to 50 mm. This rate was not maintained, however, but gradually declined to one-half the peak rate after approx. 30 min. After an initial washout period, choline was released at a rate of 2·5-5 nmol/g per min, which was equal to 1-2 × 10−6m in the superfusate. The addition of 1 × 10−5m-choline to the superfusing medium was required to maintain the stimulated ACh release at near peak rates for 90 min. When hemicholinium-3 was added to the 50 mm-KCl medium, the release of ACh reached a peak as usual but then declined to prestimulation rates.After introducing a pulse of radioactive choline in the superfusing medium, the specific radioactivity of choline and ACh in the superfusate was determined before and during stimulation with 50 mm-KCl. The specific radioactivity of released ACh was always greater than that of released choline; it decreased rapidly at the onset of stimulation, and then more gradually as stimulation proceeded. The specific radioactivity of ACh released in the initial minutes of stimulation was higher than that of ACh in the tissue before stimulation. In the last 10-20 min of stimulation the specific radioactivity of the released ACh was lower than that of the tissue ACh at the end of stimulation. The relative contributions of old and newly synthesized ACh to the releasable transmitter pool are discussed.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 18 (1971), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— Subcellular fractions were isolated from tissue incubated in [3H]choline with or without the addition of 33 mM-KCl. Radioactive and bioassayable ACh were measured in the synaptosomes, synaptosomal cytoplasm and in the vesicles. After incubation with KCI the vesicles, as isolated, contained ACh of a lower specific activity than the cytoplasmic ACh. Therefore the vesicle fraction as isolated does not represent the source of the high specific activity ACh released upon K+ stimulation. However the vesicle fraction is heterogeneous. Most of the bioassayable ACh but little of the radioactive ACh in the vesicles passed through iso-osmotic Sephadex columns. These results raise the question of the existence of vesicles which contain highly radioactive ACh but which lose it during their isolation by current methods. Different possible forms of heterogeneity are discussed.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 18 (1971), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— Guinea pig cerebral cortex slices were incubated for 60 min in a medium containing [3H]choline with or without the addition of 33 mM-KCl for the last 30 min. KC1 caused the release into the medium of large amounts of both bioassayable and radioactive ACh, while at the same time their concentrations in the tissue decreased. The specific activity (d.p.m./pmol) of the ACh released by KC1 was greater than that released in control incubations, indicating that it comes from a newly synthesized, more radioactive store. The amounts of [3H]choline, [3H]ACh and the specific activity of tissue acetylcholine reached a plateau in the tissue 30 min after the addition of isotope. However isotopic equilibrium was not achieved because the specific activity of the ACh released, with or without KC1 in the subsequent 30 min, was less than the specific activity of the ACh remaining in the tissue. This implies the existence of a pool of ACh in the tissue which is turning over very slowly or is being synthesized from a less radioactive pool of choline. This pool of ACh does not contribute substantially to that released by KC1. Levorphanol at 10−3 M, as well as the analgesically inactive stereoisomer, dextrorphan, blocked the KCl-stimulated release of both bioassayable and radioactive ACh. These drugs demonstrate the coupling of synthesis and release of ACh in cerebral cortex slices.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 41 (1983), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The convulsant barbiturate 5-(2-cyclohexylidene-ethyl)-5-ethyl barbituric acid (CHEB) stimulates the spontaneous release of endogenous and radiolabeled acetylcholine (ACh) from mouse hippocampal slices in vitro. In order to determine if the ability of CHEB to release ACh was unique to this neurotransmitter, we have studied the action of this drug in vitro on the release of both radiolabeled and endogenous putative neurotransmitter and non-transmitter amino acids in the hippocampus. Although CHEB stimulated the spontaneous release of both [3H] γ-n-aminobutyric acid (GABA) and endogenous GABA, CHEB had different effects on the spontaneous release of radiolabeled and endogenous l-glutamate and l-aspartate: l-[3H]glutamate release was inhibited by CHEB, but endogenous l-glutamate release was unaffected by the drug; l-[3H]aspartate release was not affected by CHEB, but endogenous l-aspartate release was stimulated. The spontaneous release of the amino acids l-alanine and glycine (not thought to be neurotransmitters in the hippocampus) was not affected by CHEB. The results of this study indicate that CHEB does not always stimulate the release of all putative neurotransmitters. The ability of this drug to release ACh, GABA, and l-aspartate may be the result of some specific interaction of CHEB with nerves using these neurotransmitters in the hippocampus. In addition, the results suggest some problems that may be encountered when radiolabeled substances are used to study neurotransmitter release.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Choline uptake in hippocampal synaptosomes was not inhibited by pentobarbital administration when rats were decapitated immediately upon loss of the righting reflex (3–4 min) even though it was inhibited at later times post-injection, when the rats were still unable to right themselves. Choline uptake was increased when the animals were decapitated at convulsion after an injection of picrotoxin, high doses of bicuculline, or one of the convulsant barbiturates. However, another convulsant barbiturate, as well as strychnine and lower doses of bicuculline, did not increase choline uptake even though the animals also convulsed. Thus loss of righting reflex or convulsion is not directly correlated with changes in choline uptake. At 7 min after injection, levels of pentobarbital in the hippocampus (and other brain regions) were correlated with the degree of inhibition of choline uptake up to about 50% inhibition; however, greater inhibition could not be achieved with much higher brain levels of the drug. Although hippocampal uptake was partially inhibited at 1 h after septal lesions, 3 h after the lesion the inhibition was no longer apparent. Inhibition was almost complete 10–12 days after the lesion. These results suggest that other factors in addition to impulse flow influence choline uptake.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 104 (1991), S. 22-26 
    ISSN: 1432-2072
    Keywords: Barbiturates ; Phenobarbital ; Functional tolerance ; Hypothermia ; Food intake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Phenobarbital elicits a hypothermic effect in rats. To determine if functional tolerance develops to this effect on temperature, rats were treated twice daily with IP injections of sodium phenobarbital (PheB) or saline. The PheB doses were increased over 21 days and then were held constant for another 23 days. On the next day (day 45) animals from both groups were given 80, 110 or 160 mg/kg PheB IP and the decrease in rectal temperature after 2 h was determined. Animals were decapitated after the temperature measurement and brain PheB levels were determined. A 1.51-fold shift in the relationship between brain level and response was found for the group given chronic PheB. These results show functional tolerance occurs to the hypothermic effect of PheB. This experiment was done in animals that were on a restricted food regimen. Rats given chronic PheB lost more weight than the group given chronic saline unless extra food was provided. We found that this occurred because the rats given chronic PheB lost more food through the wire cage floor than rats given chronic saline.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1106
    Keywords: Heterozygous weaver mice ; Midbrain dopamine neurons ; TH immunochemistry ; Cell count ; Striatum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The phenotypic effect of theweaver mutation in the ventral midbrain of homozygous mutants is associated with the progressive loss of dopaminergic neurons. To discover whether the number of mesencephalic dopaminergic cells is altered in weaver heterozygotes (wv/+), we studied mice between 20 and 365 days of age. We counted tyrosine hydroxylase (TH)-immunopositive cells in the substantia nigra (SN), retrorubral nucleus (RRN), and ventral tegmental area (VTA), and measured cross-sectional areas of neuronal somata in the SN ofwv/+ and age-matched wild-type controls (+/+). The number of TH-positive cells in thewv+ ventral midbrain was on average 13% lower than normal. Cell loss was detected selectively in the SN (12%) and VTA (23%). The areas of somatic profiles in thewv/+ nigral neurons were on average reduced by 9.8%. The neuronal losses in the SN and VTA correlated with a 13.8% reduction in dopamine level in the ventral striatum inwv/+ mice at 14–16 months of age. Our findings imply that a single dose of theweaver gene in the mouse is associated with cellular damage leading to a chronic deficiency in the mesostriatal dopaminergic system.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 17 (1970), S. 327-337 
    ISSN: 1432-2072
    Keywords: Morphine ; Levorphanol ; Narcotics ; Invertebrates ; Behavior
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Methods for the measurement of the light responses of Artemia nauplii and adults are described. Although no effects of levorphanol were found on the positive phototaxis of nauplii, this compound inhibited and partially reversed the negative phototaxis of adults. Levorphanol was also effective in adults after removal of the compound eyes, indicating that it probably acts on the median eye or its central connections in adults. Methadone and dextrorphan (the inactive stereoisomer of levorphanol) caused similar effects in adults, but morphine was inactive. Pentobarbital inhibited the negative movement but induced very little positive phototaxis. Attempts to reverse the effect of levorphanol with nalorphine pretreatment were unsuccessful. Attempts to develop tolerance to levorphanol were also unsuccessful; the shrimp died, apparently as a result of an increasing effect of the drug with time.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1573-6903
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The K-stimulated release of [3H]ACh from rat midbrain slices prelabeled by incubation with [3H]choline was dependent on extracellular Ca. Phenobarbital inhibited the K-stimulated [3H]ACh release and the IC50 was equal to that found for K-stimulated endogenous ACh release. These results support the suggestion that barbiturates primarily inhibit the Ca-dependent stimulated release of ACh and affect ACh synthesis only indirectly. K-Stimulated release of [3H]5-HT was also inhibited by removing Ca from the medium or by adding phenobarbital which further supports the effects of barbiturates on the depolarization-induced release process. Fluoxetine, an inhibitor of 5-HT uptake, increased the amount of [3H]5-HT found in the medium but did not fully block the uptake of [3H]5-HT in this slice preparation.
    Type of Medium: Electronic Resource
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