Linked Life Data

17207474

Source:http://linkedlifedata.com/resource/pubmed/id/17207474

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-1-29
pubmed:abstractText
Many studies suggest that the 5-HT6 receptors are involved, along with other 5-HT receptors, in the pathophysiology and pharmacotherapy of schizophrenia. It is a putative therapeutic target of atypical antipsychotic drugs, notably clozapine, as well as some other psychotropic agents. Preferential potentiation of dopamine (DA) efflux in the medial prefrontal cortex (mPFC) and hippocampus (HIP) has been suggested to contribute to the ability of atypical antipsychotic drugs (APDs), e.g. clozapine, risperidone, olanzapine and ziprasidone, to improve cognitive function in schizophrenia. The present study demonstrated that SB-399885, a selective 5-HT6 receptor antagonist, at doses of 3 and 10 mg/kg, had no effect on cortical DA release in freely moving rats. However, both doses of SB-399885 slightly but significantly increased DA release in the HIP. Of particular interest, SB-399885, 3 mg/kg, significantly potentiated the ability of a typical antipsychotic drug haloperidol, a D2 receptor antagonist, at a dose of 0.1 mg/kg, to increase DA release in the HIP but not the mPFC. The atypical antipsychotic drug risperidone, a multireceptor antagonist, which lacks 5-HT6 receptor antagonist properties, at doses of 0.1, 0.3 and 1.0 mg/kg, produced a bell-shaped dose response effect on DA efflux in the mPFC and HIP. SB-399885 potentiated risperidone (1.0 mg/kg)-induced DA efflux in both regions. The increase in the HIP, but not the mPFC, DA efflux by 0.3 mg/kg risperidone was also potentiated by SB-399885, 3 mg/kg. These results suggest that the combined blockade of 5-HT6 and D2 receptors may contribute to the potentiation of haloperidol- and risperidone-induced DA efflux in the mPFC or HIP. The present data provides additional evidence in support of a possible therapeutic role for 5-HT6 receptor antagonism, as an addition on therapy, to enhance cognitive function in schizophrenia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
1134
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
70-8
pubmed:meshHeading
pubmed-meshheading:17207474-Animals, pubmed-meshheading:17207474-Dopamine, pubmed-meshheading:17207474-Dopamine Antagonists, pubmed-meshheading:17207474-Dose-Response Relationship, Drug, pubmed-meshheading:17207474-Drug Synergism, pubmed-meshheading:17207474-Extracellular Fluid, pubmed-meshheading:17207474-Haloperidol, pubmed-meshheading:17207474-Hippocampus, pubmed-meshheading:17207474-Male, pubmed-meshheading:17207474-Microdialysis, pubmed-meshheading:17207474-Piperazines, pubmed-meshheading:17207474-Prefrontal Cortex, pubmed-meshheading:17207474-Rats, pubmed-meshheading:17207474-Rats, Sprague-Dawley, pubmed-meshheading:17207474-Receptors, Dopamine D2, pubmed-meshheading:17207474-Receptors, Serotonin, pubmed-meshheading:17207474-Risperidone, pubmed-meshheading:17207474-Serotonin, pubmed-meshheading:17207474-Serotonin Antagonists, pubmed-meshheading:17207474-Sulfonamides, pubmed-meshheading:17207474-Synaptic Transmission
pubmed:year
2007
pubmed:articleTitle
5-HT6 receptor antagonist SB-399885 potentiates haloperidol and risperidone-induced dopamine efflux in the medial prefrontal cortex or hippocampus.
pubmed:affiliation
Psychopharmacology Division, Psychiatry Department, Vanderbilt University School of Medicine, 1601 23rd Ave. South, Suite 306, Nashville, TN 37212, USA. zhu.li@vanderbilt.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't