Source:http://linkedlifedata.com/resource/pubmed/id/19744833
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2009-10-5
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| pubmed:abstractText |
Bi-acetylated l-stepholidine (l-SPD-A), a novel derivate of l-stepholidine (l-SPD), possesses a pharmacological profile of D(1)/5-HT(1A) agonism and D(2) antagonism. In the present study, we examined the potential antipsychotic effect of l-SPD-A in a phencyclidine (PCP)-induced rat model of schizophrenia. Pretreatment with l-SPD-A blocked acute PCP-induced hyperlocomotion and reversed prepulse inhibition (PPI) deficits. Chronic l-SPD-A administration (i.p., 10mg/kg/day for 14 days) improved social interaction and novel object recognition impairments in rats that were pretreated with PCP (i.p., 5mg/kg/day for 14 days). Moreover, in a conditioned avoidance response (CAR) test, l-SPD-A, with either i.p. or oral administration, significantly decreased active avoidance without affecting the escape response of rats. Importantly, compared to that of the parent compound l-SPD, l-SPD-A showed stronger suppression of CARs. Lastly, using a [(35)S]GTPgammaS binding assay, we demonstrated that l-SPD-A improved impaired dopamine D(1) receptor function in the prefrontal cortex (PFC) in chronic PCP-treated rats. Taken together, these results indicate that l-SPD-A was not only effective against the hyperactivity, but also improved the sensorimotor gating deficit, social withdrawal and cognitive impairment in an animal model of schizophrenia. The present data suggest that l-SPD-A, a potential neurotransmitter stabilizer, is a promising novel candidate drug for the treatment of schizophrenia.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antipsychotic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Berberine,
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine 5'-O-(3-Thiotriphosphate),
http://linkedlifedata.com/resource/pubmed/chemical/Phencyclidine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Dopamine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/stepholidine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
1573-2509
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
115
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
41-9
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| pubmed:dateRevised |
2010-9-2
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| pubmed:meshHeading |
pubmed-meshheading:19744833-Acoustic Stimulation,
pubmed-meshheading:19744833-Analysis of Variance,
pubmed-meshheading:19744833-Animals,
pubmed-meshheading:19744833-Antipsychotic Agents,
pubmed-meshheading:19744833-Avoidance Learning,
pubmed-meshheading:19744833-Berberine,
pubmed-meshheading:19744833-Disease Models, Animal,
pubmed-meshheading:19744833-Dose-Response Relationship, Drug,
pubmed-meshheading:19744833-Drug Interactions,
pubmed-meshheading:19744833-Exploratory Behavior,
pubmed-meshheading:19744833-Guanosine 5'-O-(3-Thiotriphosphate),
pubmed-meshheading:19744833-Inhibition (Psychology),
pubmed-meshheading:19744833-Interpersonal Relations,
pubmed-meshheading:19744833-Locomotion,
pubmed-meshheading:19744833-Male,
pubmed-meshheading:19744833-Phencyclidine,
pubmed-meshheading:19744833-Radioligand Assay,
pubmed-meshheading:19744833-Rats,
pubmed-meshheading:19744833-Rats, Sprague-Dawley,
pubmed-meshheading:19744833-Receptors, Dopamine,
pubmed-meshheading:19744833-Receptors, Serotonin,
pubmed-meshheading:19744833-Recognition (Psychology),
pubmed-meshheading:19744833-Schizophrenia,
pubmed-meshheading:19744833-Startle Reaction
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| pubmed:year |
2009
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| pubmed:articleTitle |
Evaluation of the antipsychotic effect of bi-acetylated l-stepholidine (l-SPD-A), a novel dopamine and serotonin receptor dual ligand.
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| pubmed:affiliation |
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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