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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1996-9-20
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pubmed:abstractText |
The high selectivity of the phencyclidine derivative PRE-084 for sigma (sigma) sites is demonstrated. We previously reported that this compound is able to markedly attenuate the impairment of learning induced in mice by the non-competitive NMDA antagonist MK-801, and the cholinergic nicotinic antagonist mecamylamine. In this study, we examined the effect of PRE-084 on the impairment of learning induced by acute administration of the calcium channel antagonist nimodipine. Nimodipine (0.3 mg/kg i.p.) impaired the spontaneous alternation behaviour in a Y-maze, decreased the step-down latency (SDL) in a passive avoidance task, and altered place learning and retention in a water-maze paradigm, with no marked effect on the motility observed using an open-field test. Preadministration of PRE-084 resulted in an attenuation of the impairment of alternation, in the 0.3-1 mg/kg s.c. range, in a marked increase in SDL, at 1-3 mg/kg, and improved place learning and retention in the water-maze, at 1 mg/kg. The effects on alternation behaviour and passive avoidance were completely prevented by co-administration of the purported sigma antagonist BMY-14802 (10 mg/kg i.p.), implicating the sigma sites. These results confirm the beneficial effect of the sigma ligand PRE-084 on pharmacological models of learning impairments, and indicate that sigma sites may modulate Ca2+ fluxes through VDCC, which may in turn bear some as yet unknown relationship to the previously described interaction with neurotransmitter systems.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:issn |
0300-9564
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
102
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1-18
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8785020-Animals,
pubmed-meshheading:8785020-Avoidance Learning,
pubmed-meshheading:8785020-Behavior, Animal,
pubmed-meshheading:8785020-Dose-Response Relationship, Drug,
pubmed-meshheading:8785020-Male,
pubmed-meshheading:8785020-Maze Learning,
pubmed-meshheading:8785020-Mice,
pubmed-meshheading:8785020-Mice, Inbred Strains,
pubmed-meshheading:8785020-Morpholines,
pubmed-meshheading:8785020-Nimodipine,
pubmed-meshheading:8785020-Reaction Time,
pubmed-meshheading:8785020-Vocalization, Animal
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pubmed:year |
1995
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pubmed:articleTitle |
Prevention of nimodipine-induced impairment of learning by the selective sigma ligand PRE-084.
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pubmed:affiliation |
I.N.S.E.R.M. U. 336, Montpellier, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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