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  • 1
    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: A push-pull cannula technique was used to study the in vivo release of endogenous GABA in the rat substantia nigra. Intranigral application of both dopamine (DA) and apomorphine produced biphasic changes in the rate of endogenous GABA release. The presence of 10 μM-DA in the perfusion medium increased GABA release (140%). At 25 μM-DA, both stimulation and inhibition of the nigral GABA release were observed. Higher concentrations of DA produced a decrease of the GABA release (50%). A small amount of apomorphine (10 μM in the perfusion medium) resulted in a decrease in GABA release (75%). Application of 25 μM-apomorphine produces opposite effects, similar to those observed after addition of 25 μM-DA. We observed an enhanced GABA release from the substantia nigra at 100 μM-apomorphine in the perfusion medium (360%). The presence of 5 μM-haloperidol produced a small decrease in the rate of GABA release (80%). Both the inhibitory effect of 25 μM-DA and the excitatory effect of 100 μM-apomorphine could be blocked by haloperidol added to the perfusion medium. Dibutyryl cyclic AMP (1.5 mM) and 2-amino-6, 7-dihydroxyl(1, 2, 3, 4) tetrahydronapthalene (ADTN) (50 μM) added to the perfusion medium produced an inhibition of nigral GABA release (55% and 35% respectively) similar to that observed after addition of 50 μM-DA. The amounts of lysine and ethanolamine (measured with GABA concurrently) released into the perfusion medium did not change in most of the experiments. The changes in the rates of release of these compounds that were observed in some experiments were either in the same or in the opposite direction of the change in GABA release. These results suggest that dopaminergic processes within the substantia nigra affect GABA-ergic neurotransmission and that DA and apomorphine have different effects on GABA release.
    Type of Medium: Electronic Resource
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  • 2
    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: A push-pull cannula technique was used to study the in vivo release of endogenous GABA from the striaturn of chloral hydrate anaesthesized rats. The GABA in the perfusate was isolated with hplc and fluorimetrically detected (detection limit 0.6 pmol, signalhoke = 3). The mean resting release of GABA under steady state conditions was 1.62 ± 0.09 pmo/min (n = 180, ± s.E.M.). GABA release was increased after addition of depolarizing amounts of potassium to the perfusion medium. Inhibition of GABA synthesis with 3-mercaptopropionic acid (MPA, 0.5 mM) or blockade of the neuronal activity with tetrodotoxin (TTX, 0.2 μM) diminished the spontaneous release of GABA. MPA, but not TTX, reduced the potassium-induced increase in GABA release. Striatal GABA release was decreased by local application of muscimol (l0 μM) but enhanced by picrotoxin (100 μM); the latter counteracted the effect of muscimol. Intrastriatally applied serotonin (100 μM) did not affect the rate of endogenous GABA release. Oxotremorine (25 μM) added to the perfusion medium slightly increased the striatal GABA release. This effect was blocked both by locally applied atropine (100 μM) and haloperidol (5 μM). The latter two drugs did not themselves affect the rate of GABA release. Perfusion with morphine (100 μM) inhibited striatal GABA release. This effect was not influenced by haloperidol, but was no longer observed in the presence of nalorphine (10 μM) which itself did not alter GABA release. These results indicate that GABA released from the striatum is, at least in part, of neuronal origin and that the spontaneous GABA release can be affected by various neuromodulators (including GABA, enkephalins, and acetylcholine).
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 33 (1979), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract– The GABA content of the spinal cord and of approx 70 discrete rat brain nuclei is measured with a simple rapid semi-automated fluorimetric assay, after prevention of post-mortem effects with 3-mercaptopropionic acid. We found that microwave irradiation produced decreases in the GABA contents of the microdissected zona reticulata of the substantia nigra, indicating that microwave fixation is not suitable to measure GABA levels in microdissected brain nuclei. In approx 70% of the nuclei in the anterior half of the brain the GABA concentration was found to be between 41 and 90nmol GABA/mg protein. The GABA content varied from 11 to 40 nmol GABA/mg protein in the posterior half of the brain. High GABA levels were found in some hypothalamic nuclei, the globus pallidus and eminentia mediana. An extremely high GABA level was found in the zona reticulata of the substantia nigra. GABA is unevenly distributed in the striatum. The highest concentration was found in the caudal part and in the ventral region at any level of the striatum. In the spinal cord the highest concentration of GABA was in the sacral region.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 32 (1979), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A sensitive GABA assay using HPLC coupled with fluorimetric detection with o-phthalaldehyde is described. GABA, lysine and ethanolamine can be measured within approx 12 min. The detection limits for these compounds (signal/noise = 3) is 0.67 pmol, 1.8 pmol and 0.73 pmol respectively. Using this assay the in vivo release of GABA from rat substantia nigra was studied with a push-pull perfusion technique.A pronounced increase in the rate of endogenous GABA release was observed after addition of depolarizing amounts of K+ to the perfusion medium, whereas the concentrations of lysine and ethanolamine in the perfusate did not change. This enhanced release of GABA was not diminished after omission of Ca2+ and Mg2+ from the medium. Increasing the Mg2+ concentration and leaving out Ca2+ however, resulted in a marked depression in the K+-induced GABA release.Electrical stimulation of the striatum also produced an increase in release of GABA from the substantia nigra.Inhibition of glutamic acid decarboxylase (with 3-mercaptopropionic acid) caused an immediate decrease in GABA release. Inhibition of GABA transminase (with aminooxyacetic acid) leads to an increased release of GABA after approx 15 min.These findings suggest that the technique is suitable for measuring neuronal release of endogenous GABA in vivo
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 31 (1978), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— A simple and rapid semiautomated assay for GABA in central nervous tissue is described. The method is based on a simple manual procedure of isolating GABA from tissue extracts on small CM Sepharose Cl 6B columns, followed by an automated fluorimetric detection (continuous flow system) with o-phthalaldehyde (OPA) and β-mercapto-ethanol (β-ME) at an alkaline pH. GABA is separated from other compounds that fluoresce in our detection system. By using low concentration of OPA and β-ME and allowing only a short reaction time with these reagents, the detection is specific towards GABA. The detection limit of the assay is 1 nmol.A procedure is described for the prevention of postmortem GABA increase in rat and mouse brain by intravenous injection of 3-mercapto-propionic acid (1.2 nmol/kg) 2min before decapitating the animal. This treatment and microwave irradiation result in similar GABA levels in mouse brain and substantia nigra tissue from rat brain. We found a great conformity in regional GABA levels in the rat and the mouse brain.
    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
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 92 (1987), S. 127-130 
    ISSN: 1432-2072
    Keywords: Antidepressants ; Behavioural despair ; Tail suspension test ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of several types of antidepressants in a recently developed “behavioural despair” model, the tail-suspension test, are described. Drug effects on the automatically recorded duration of immobility and power of movements were measured in three strains of mice. Only in one strain (NMRI) did almost all antidepressants tested showed the expected reduction in duration of immobility. Tranquillizing drugs, but not stimulants, could be distinguished from antidepressants. The power of movements could not definitively be related to the pharmacological profile of the drugs tested. The use of the tail-suspension test as a rapid and highly predictive behavioural primary screen for antidepressant drugs is suggested.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-2072
    Keywords: Ultrasonic distress vocalizations ; Adult rat ; Anxiety ; Panic disorder ; Situational panic attack ; Alprazolam ; 5-HT uptake inhibitor ; Fluvoxamine ; Clomipramine ; Imipramine ; Diazepam ; Chlordiazepoxide ; Benzodiazepine ; 5-HT1A receptor agonist ; NA uptake inhibitor ; Dopamine-D2 receptor antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats may produce ultrasonic vocalizations (USV) in threatening situations. USV of adult male rats in association with aversive stimulation was evaluated as a screening method for anxiolytic drugs. The triazolobenzodiazepine alprazolam, the 5-HT uptake inhibitors fluvoxamine and clomipramine, the mixed 5-HT/NA uptake inhibitor imipramine, the full 5-HT1A receptor agonists 8-OH-DPAT and flesinoxan, the partial 5-HT1A receptor agonists buspirone, ipsapirone and BMY 7378, theα 2-adrenoceptor agonist clonidine and theα 2-adrenoceptor antagonist yohimbine reduced conditioned USV. The classical benzodiazepines (BZD) diazepam and chlordiazepoxide were ineffective or had a very low potency to decrease USV. The partial BZD receptor agonists bretazenil, alpidem and zolpidem, the BZD receptor antagonist flumazenil, the NA uptake inhibitors desipramine and maprotiline, and the 5-HT3 receptor antagonist ondansetron had no effect on conditioned USV. The dopamine-D2 receptor antagonist haloperidol reduced USV at a very high dose. In separate experiments the effects of these drugs on locomotor activity were assessed. There was, however, no direct relationship between effects on motor behaviour and USV. In conclusion, the sensitivity of conditioned USV to 5-HT uptake inhibitors and alprazolam versus the insensitivity to classical benzodiazepines and NA uptake inhibitors provides a very interesting profile, which closely resembles the psychopharmacology of panic disorder. Also the face validity of conditioned USV towards situational panic attacks is high. We therefore propose conditioned USV in adult male rats as a novel behavioural paradigm to screen for anti-panic drugs.
    Type of Medium: Electronic Resource
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