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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The hydroxyl radical is a very reactive oxygen species that damages biomolecules in the brain and in other tissues. The possible pharmacological intervention to prevent hydroxyl radical formation was studied in vivo using the microdialysis technique in brains of nonanesthetized rats. Hydroxyl radicals form stable adducts [mainly 2,3-dihydroxybenzoic acid (2,3-DHBA) and 2,5-DHBA)] via an aromatic hydroxylation reaction with salicylic acid. 2,3-DHBA was separated and quantified by HPLC and electrochemical detection. Microdialysis probes were implanted into the striatum 1 day before measurement of levels of hydroxyl radicals. The next day, the probes were first perfused for 120 min with a modified Ringer's solution containing 5 mM salicylic acid, to obtain stable baselines. Afterward, the perfusion solution was switched to another solution that in addition contained 50 mM glutamate, to stimulate radical formation. Twenty minutes later, α-phenyl-tert-butylnitrone (PBN; 100 mg/kg), selegiline (10 mg/kg), or saline was administered intraperitoneally. The glutamate perfusion produced marked two- to 2.5-fold increases in 2,3-DHBA content. Treatment with PBN significantly antagonized the rise of 2,3-DHBA level, indicating that PBN is a direct radical scavenger not only in vitro but also in vivo. Acute treatment with selegiline failed to reduce significantly the glutamate-induced radical formation. The acute experiments presented here do not support the suggestion that the neuroprotective effects of selegiline described in the literature are due to a potential hydroxyl radical scavenging property of the drug.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 78 (1989), S. 231-247 
    ISSN: 1435-1463
    Keywords: Morphine ; conditioned effects ; hyperkinesia ; stereotyped behaviour
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Morphine (15 mg/kg i.p.) produces a biphasic effect: hypokinesia, followed by hyperkinesia and stereotyped behaviour. After repeated administration, the signs of the second phase more and more predominate. In the following study, it was evaluated, to which degree “classical” pharmacodynamic tolerance to hypokinesia or, alternatively, conditioning phenomena contribute to this shift. In particular, it was studied whether not only hyperkinesia but also stereotypies could occur as conditioned responses either in the presence or in absence of morphine. Rats were conditioned 8 times with morphine (15 mg/ kg i.p.) in the presence of various, defined conditioned stimuli (auditory, olfactory and tactile), another group was “pseudoconditioned”, i.e. they were exposed to the same treatment schedule of morphine and stimuli, but with no positive association between drug and stimuli, a third group (“naive rats”) was treated with saline instead of morphine, but exposed to the same stimuli as both other groups. All groups were tested for conditioned responses in the presence of the conditioned stimuli. One series of experiments was performed with saline after a break of 2 days after the end of the conditioning period, a second series was tested with saline after a break of 7 days, a third series with morphine (15 mg/kg i.p.) after a break of 2 days, a fourth series with the same dose of morphine after a break of 7 days. The results showed that when morphine was used after a break of 2 days, “classical” pharmacodynamic tolerance, but not conditioning phenomena could explain the shift in behaviour, whereas under the three other protocols described, some conditioned behavioural effects could be observed, either in presence or in absence of morphine, at least in part of the parameters used (locomotor activation, decrease in hypokinesia, sniffing, gnawing, rearing, but not in licking). Accordingly, development of pharmacodynamic tolerance and, to a lesser degree, conditioning contribute to the shift in behaviour after repeated administration of morphine. The conditioned effects could not be attributed to any alteration in striatal or mesolimbic dopamine turnover.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 29 (1973), S. 1365-1366 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Zusammenfassung Nach Hemmung der Dopaminsynthese beschleunigte Morphin bei Ratten die Abnahme der Dopaminkonzentration im Corpus striatum. Dieser Effekt, der durch Naloxon gehemmt wurde, lässt sich durch eine Erhöhung des Dopamin-Umsatzes im Corpus striatum unter Einfluss von Morphin erklären.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 336 (1987), S. 262-266 
    ISSN: 1432-1912
    Keywords: Conditioning ; Apomorphine ; Dopamine receptors ; Stereotyped behaviour ; Akinesia ; Ptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Apomorphine, in an intermediate dose (0.18 mg/ kg s.c.) decreased dopamine turnover and produced signs generally attributed to a decrease in dopaminergic neurotransmission, e.g. ptosis and yawning, as well as signs of an increased stimulation of dopamine receptors in dopaminoceptive target neurones, e.g. stereotyped sniffing. In contrast, the former signs were exclusively observed after smaller doses and the latter after larger doses of apomorphine. Since it had been shown in previous studies that these signs, except yawning, could be conditioned in association with discriminative stimuli in the environment, the present study using conditioning experiments with this intermediate dose aimed at determining, 1. the time course of each conditioned response, 2. the interaction of conditioned and unconditioned responses, and 3. the conditions under which hypokinesia occurred. In each series, conditioned animals were compared with pseudoconditioned controls. Rats were conditioned for 8 days with apomorphine, and on day 9, treated with saline in presence of the conditional stimuli (a test cage in combination with acoustic and olfactory stimuli). In contrast to pseudoconditioned controls, ptosis and stereotyped behaviour were observed in conditioned rats, sometimes occurring alternatingly. These signs closely resembled the direct, unconditioned pharmacological effects. In addition, akinesia occurred after conditioning, although it was never manifest as a pure drug response, nor during the conditioning period. In contrast, yawning was observed in pseudoconditioned as well as in conditioned rats, although slightly more frequently in the former animals. Subsequently, the rats were again conditioned (or pseudoconditioned) on days 10–14 with apomorphine and both groups tested with the same dose (0.18 mg/kg) of apomorphine in the presence of the conditional stimuli. Both ptosis and stereotypies were significantly enhanced in conditioned animals, indicating synergistic interactions between conditioned and direct, pharmacological behavioural effects. In all cases the conditioned effects lasted for about 30 min. The results show that, after conditioning with an intermediate dose of apomorphine, both signs typical of a low dose of apomorphine and those characteristic of a large dose can be conditioned and sometimes occur alternately.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 343 (1991), S. 559-567 
    ISSN: 1432-1912
    Keywords: Conditioning ; Apomorphine ; EEG ; Stereotyped behaviour
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The possible conditioning of pharmacological effects of apomorphine on the electroencephalogram was studied using telemetric recordings in rats. Previous studies have shown that apomorphine-induced stereotyped behaviour can be conditioned: after repeated pairings of defined stimuli with the drug effect, the presentation of the external stimuli alone elicited stereotype sniffing, licking, and gnawing. Since apomorphine, an agonist at dopamine receptors, also produces a characteristic EEG pattern with an increase of power in the alpha-1 band, the possibility that this effect could also be conditioned was studied. In fact, conditioning with a dose of 0.5 mg/kg apomorphine (s. c.) led to a significant increase in the number of short-lasting episodes with enhancement of the power in the alpha-1 range in the presence of the conditioned stimuli, according to a comparison of the results obtained in the conditioned group and those of the controls (“pseudoconditioned”). Moreover, behavioural studies were performed simultaneously in order to find possible correlations between conditioned effects on EEG and conditioned alterations in behaviour. In general, a fair correlation between the increase of power in the alpha-1 band and stereotyped behaviour was found. This was also the case during extinction, when the conditioned stimuli were repeatedly uncoupled from apomorphine administration: both behavioural parameters and EEG alterations showed similar time-courses and had almost disappeared during the fourth extinction session.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 335-340 
    ISSN: 1432-1912
    Keywords: Key words d-Amphetamine ; Stereotyped behaviour ; Sensitization ; EEG ; Dopamine receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract After repeated administration of cocaine or d-amphetamine, a sensitization to their behavioural effects is frequently observed instead of a tolerance. In a previous study, it was shown that a moderate dose of d-amphetamine produced a pattern of EEG power spectrum which indicated a selective activation of D1-like dopamine receptors, whereas a larger dose induced a selective increase of power in the alpha-1 frequency band and, to a lesser degree, in the alpha-2 band, suggesting an additional activation of D2-like receptors. Furthermore, it was recently found that under a certain dosage and schedule, cocaine could produce a shift from a D1-characteristic to a D2-like EEG pattern. It was now studied, if the same is true for d-amphetamine. This drug was administered on 4 subsequent days (0.6 mg/kg i.p.); after an interval of 3 days, the same dose was administered. After repeated, but not a single administration, increases in the power of the alpha-1 and alpha-2 frequency bands were observed, suggesting a shift from activation of D1-like to additional activation of D2-like receptors. This shift was accompanied by a slight enhancement in stereotyped behaviour (sniffing). After a lower dose (0.2 mg/kg), no EEG effect could be observed, neither after a single nor after repeated administration.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1912
    Keywords: Key words Cocaine ; D-Amphetamine ; Dopamine release ; Sensitization ; Conditioning mechanisms ; Non-associative mechanisms ; Locomotor activity ; Stereotyped behaviour
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In parallel studies, the contribution of non-associative and associative mechanisms to the development of sensitization to the effects of cocaine and D-am-phetamine on locomotor activity and stereotyped behaviour were tested. Rats were pretreated with cocaine, 10mg/kg s.c. twice, D-amphetamine 1.5mg/kg s.c. once or with saline. During the pretreatment period, one group of rats was administered the drug in positive temporal association with conditional stimuli (CS) (‘associative’), another group in negative temporal association with the CS (‘non-associative’), a saline pretreated control group was exposed to the CS but administered the drug only during the test (‘naive’). On the test day, 7 days after the last drug administration, in the cocaine-sensitized group, cocaine produced the largest locomotor stimulation and the highest scores of stereotypies (mainly sniffing) in the ‘associative’ group, significantly smaller effects in the ‘non-associative’ group, and the smallest effects in the ‘naive’ group. The stereoypies (mainly licking) produced by D-amphetamine in the amphetamine-sensitized group on the test day, 7 days after the last drug administration, were also most pronounced in the ‘associative’ group, less pronounced in the ‘non-associative’ group and least in the ‘naive’ group, whereas the opposite sequences of intensities were found with regard to locomotor activation. The observations in D-amphetamine-treated groups suggest that there is a negative correlation between locomotor activity and stereotyped licking. Estimation of the extracellular dopamine using microdialysis in the striatum showed no significant differences between the three cocaine groups in the moderate increases. In contrast, after D-amphetamine treatment, the strong increases in dopamine were most pronounced in the ‘associative’ group, significantly less in the ‘non-associative’ group and even less in the ‘naive’ group. The biochemical findings in the D-amphetamine-pretreated animals are apparently related to the pronounced stereotyped licking observed in these animals which is probably induced in the striatum, whereas locomotor activation and sniffing are probably mediated elsewhere and therefore are not reflected biochemically in the striatum.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 296 (1977), S. 249-254 
    ISSN: 1432-1912
    Keywords: Alpha-motoneurones ; Extensor ; Specific effects of narcotics ; Morphine ; Apomorphine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Specific effects of narcotics (opiates) were studied on rat extensor alpha-motoneurones. The animals were anaesthetized with halothane, artificially ventilated and immobilized with N,N′-diallyl nortoxiferinium-HCl. The alpha-motoneurones were activated by tetanic stimulation of the cut ipsilateral gastrocnemius-soleus (GS) nerve. Morphine (2 and 4 mg/kg) administered intravenously, significantly increased the frequency of reflex discharges. In most of the neurones tested, naloxone (0.25 mg/kg) given intravenously, abolished the effect of morphine. In some neurones, however, naloxone induced a further activation. The dose of naloxone employed was ineffective when given alone. The effect of morphine was mimicked by an intravenous injection of levorphanol (1 mg/kg), but not by an equimolar dose of the stereoisomer dextrorphan, which suggests that the activating effect on alpha-motoneurones is a specific one. An intraperitoneal injection of apomorphine (1 mg/kg) reduced the effect of morphine. The effect of narcotics on alpha-motoneurones parallels narcotic-induced catalepsy and muscular rigidity, with regard to dose-dependence as well as to the antagonism of naloxone and apomorphine, and suggests that both catalepsy and muscular rigidity are mainly due to an activation of extensor alpha-motoneurones. Since this activation can be inhibited by spinalization of the rats, it can be concluded that the activation is due to a supraspinal action of morphine, resulting in a decreased dopaminergic neurotransmission in the brain.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 29 (1973), S. 826-827 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Zusammenfassung Bei Mäusen erhöhte Pentobarbital den Serotoningehalt des Gehirns, ein Effekt, der sich durch eine Verminderung der Umsatzgeschwindigkeit bei unveränderter Synthese des Serotonins erklären lässt.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 32 (1976), S. 1558-1559 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Penfluridol, a neuroleptic with diphenylbutyl piperidine structure, blocked the dopamine-sensitive adenylate cyclase in homogenates of corpus striatum and substantia nigra of rats, probably by a competitive antagonism versus dopamine.
    Type of Medium: Electronic Resource
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