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  • 1
    Electronic Resource
    Electronic Resource
    Effects of the Uncompetitive NMDA Receptor Antagonist Memantine on Hippocampal Long-term Potentiation, Short-term Exploratory Modulation and Spatial Memory in Awake, Freely Moving Rats (1996)
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 8 (1996), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Chronic treatment of adult male F-344 rats (9–12 months old) with therapeutically relevant doses of memantine (30 mg/kg/day in chow for 〈8 weeks) increased the maintenance of long-term potentiation of field excitatory postsynaptic potentials from perforant path—granule cell hippocampal synapses recorded in the fascia dentata in vivo. In contrast, there was no effect of memantine on baseline synaptic responses or population spikes. Likewise, short-term exploratory modulation of these hippocampal evoked responses was not different between memantine-treated and control rats. Both groups of rats were able to learn the spatial version of the Morris water task equally well, but the memantine-treated group showed a strong tendency to show more selective spatial search patterns in the training quadrant of the water pool during a final probe trial. As such, these studies provide the first electrophysiological evidence that memantine can increase the durability of synaptic plasticity and provide preclinical confirmation of the cognitive improvement seen with memantine in the treatment of demented patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.1996.tb01241.x
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  • 2
    Electronic Resource
    Electronic Resource
    Brain Penetration and In Vivo Recovery of NMDA Receptor Antagonists Amantadine and Memantine: A Quantitative Microdialysis Study (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 637-642 
    Details
    ISSN: 1573-904X
    Keywords: aminoadamantanes ; in vivo recovery ; microdialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To determine free brain concentrations of the clinically used uncompetitive NMDA antagonists memantine and amantadine using microdialysis corrected for in vivo recovery in relations to serum, CSF and brain tissue levels and their in vitro potency at NMDA receptors. Methods. Microdialysis corrected for in vivo recovery was used to determine brain ECF concentrations after steady-state administration of either memantine or amantadine. Additionally CSF, serum, and brain tissue were analyzed. Results. Following 7 days of infusion of memantine or amantadine (20 and 100 mg/kg/day respectively) whole brain concentrations were 44-and 16-fold higher than free concentrations in serum respectively. The free brain ECF concentration of memantine (0.83 ± 0.05 μM) was comparable to free serum and CSF concentrations. In case of amantadine, it was lower. A higher in vivo than in vitro recovery was found for memantine. Conclusions. At clinically relevant doses memantine reaches a brain ECF concentration in range of its affinity for the NMDA receptor and close to its free serum concentration. This is not the case for amantadine and different mechanisms of action may be operational.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018856020583
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  • 3
    Electronic Resource
    Electronic Resource
    Ethanol discrimination in the rat: lack of modulation by restraint stress and memantine (1999)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 359 (1999), S. 117-122 
    Details
    ISSN: 1432-1912
    Keywords: Key words Ethanol ; Restraint stress ; NMDA receptor complex ; Memantine ; Drug discrimination ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is a large body of experimental evidence that both stress and N-methyl-d-aspartate (NMDA) receptor antagonists may alter acute behavioural effects of ethanol. Notably, an uncompetitive, low-affinity NMDA receptor antagonist, memantine, has been recently claimed to possess anti-craving properties in rats with a long-term history of ethanol consumption. The aim of the present study was to assess the effects of restraint stress and memantine on the dose-response curve of ethanol discrimination. Rats were trained to discriminate 1 g/kg ethanol from saline in the two-lever drug discrimination procedure. When ethanol discrimination was acquired, the subjects were exposed to 30-min sessions of acute restraint stress, and different doses of ethanol (0.25, 0.5 or 1 g/kg) or saline were administered. In subsequent experiments the effects of memantine (2.25 or 4.5 mg/kg) on the cueing effects of ethanol were tested. Neither the stress sessions nor memantine influenced the ethanol discrimination dose-response curve. Moreover, the stress did not alter the rate of responding. However, both doses of memantine tended to increase the rate of responding when given in combination with lower doses of ethanol (0.25–0.5 g/kg). In contrast, 4.5 mg/kg memantine decreased the response rate when combined with 1 g/kg ethanol. These results suggest that: (1) pre-exposure to acute restraint stress or memantine does not affect the dose-response curve of ethanol discrimination; (2) memantine given in combination with low doses of ethanol may stimulate operant behaviour in the food-reinforced drug discrimination procedure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005330
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  • 4
    Electronic Resource
    Electronic Resource
    Ethanol and N-methyl-D-aspartate receptor complex interactions: a detailed drug discrimination study in the rat (1998)
    Springer
    Psychopharmacology 135 (1998), S. 44-51 
    Details
    ISSN: 1432-2072
    Keywords: Key words Drug discrimination ; Rat ; Ethanol ; NMDA receptor ; AMPA receptor ; Dizocilpine ; Memantine ; Phencyclidine ; N-allyl-normetazocine ; Pentazocine ; Arcaine ; Polyamine site ligand ; Glycine site ligand
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The discriminative stimulus properties of compounds that interact with the NMDA receptor complex were investigated in rats trained to discriminate ethanol from saline. Male Wistar rats were trained in a two-lever operant drug discrimination paradigm to make differential responses [fixed ratio 10 (FR10)] for food after ethanol (1 g/kg IP; 12% v/v ethanol solution) and saline vehicle injections. Drug effects were assessed by means of generalization and antagonism tests. In the generalization tests, the noncompetitive NMDA antagonists acting at the ion channel dizocilpine, memantine, phencyclidine (PCP) and the sigma1 receptor agonists (+)-pentazocine and (+)-N-allyl-normetazocine (NANM) dose-dependently generalized for ethanol, whereas the α-amino-3-hydroxy- 5-methyl-4-isoxazole-propionate (AMPA) antagonist GYKI 52466, the glycine antagonists L-701,324 and MRZ 2/502, the polyamine site antagonist arcaine and the polyamine site ligand spermidine, did not. Our results show that the noncompetitive NMDA antagonists fully substitute dose-dependently for ethanol in a drug-discrimination task. The ethanol-like discriminative stimulus effects of PCP, pentazocine and NANM, which are also sigma receptor ligands, are likely to be attributed to their activity at NMDA receptors. We therefore assume that some of the acute effects of ethanol are mediated via NMDA receptor antagonism at the PCP binding site.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050484
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  • 5
    Electronic Resource
    Electronic Resource
    A stimulatory effect of intraaccumbens injections of noradrenaline on the behavior of rats in the forced swim test (1985)
    Springer
    Psychopharmacology 87 (1985), S. 119-123 
    Details
    ISSN: 1432-2072
    Keywords: Nucleus accumbens ; Noradrenaline ; Dopamine ; Serotonin ; Monoaminergic agonists ; Open field locomotor activity ; Forced swim test ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intraaccumbens injections of catecholamines noradrenaline and dopamine, though not of serotonin, stimulated locomotion by rats in an open field, 10–15 min later. Similar effects were observed 5 min after microinjection of apomorphine whereas clonidine only attenuated locomotor activity. On the other hand, intraaccumbens administration of phenylephrine, isoproterenol and quipazine, in doses similar to an effective dose of noradrenaline, did not alter rat open field behavior. The escape-directed activity of rats in the forced swim test (FST) was stimulated 5 min after local administration of noradrenaline, phenylephrine, isoproterenol or apomorphine only. No effects in the FST were observed 15 min after noradrenaline injection or after intracaudate noradrenaline administration. The stimulatory effects of intraaccumbens noradrenaline injection in the FST were antagonized by the local pretreatment of rats with phentolamine, though not with propranolol. Accordingly, it is possible to conclude that both catecholamines, but not serotonin, play complex and probably distinct roles within the nucleus accumbens in the stimulation of activity by rats in the FST and the open field test.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431791
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