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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0001554,
umls-concept:C0013030,
umls-concept:C0016904,
umls-concept:C0022614,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0036751,
umls-concept:C0162783,
umls-concept:C0205098,
umls-concept:C0205171,
umls-concept:C0205341,
umls-concept:C0443199,
umls-concept:C1280500,
umls-concept:C1521797
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pubmed:issue |
2
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pubmed:dateCreated |
1997-10-28
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pubmed:abstractText |
Cognitive functions regulated by the prefrontal cortex are sensitive to changes in dopaminergic and serotoninergic transmission. The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine influences dopaminergic transmission and induces psychotic symptoms in normal and schizophrenic individuals. This study examined the effect of single and repeated ketamine (25 mg/kg, i.p.) administration on extracellular levels of dopamine, GABA and the serotonin metabolite 5-hydroxyindoleacetic (5-HIAA) acid in the medial prefrontal cortex using in vivo microdialysis in conscious rat. In line with earlier studies, we observed a transient five-fold increase in dopamine release following single ketamine administration in drug naive animals. However, we also observed a two-fold increase in basal dopamine levels and an almost complete attenuation of the ketamine-induced increase in dopamine release in animals pre-treated with ketamine once daily for 7 days. Extracellular 5-HIAA levels were increased by ketamine in both drug naive and even more enhanced in ketamine-pre-treated animals but without a change in basal 5-HIAA levels. GABA levels were unaffected by either single or repeated ketamine administration. We demonstrate evidence for a differential effect of single and repeated ketamine administration on dopamine, serotonin and GABA transmission in the medial prefrontal cortex. We provide new evidence for a complex adaptation of neurotransmission following repeated NMDA receptor blockade whereby in the presence of increased basal dopamine levels the ketamine-induced increase in dopamine is attenuated and the increase in 5-HIAA is enhanced. It appears from our results that ketamine pre-treatment reduces the dynamics of dopaminergic transmission in the prefrontal cortex and may possibly alter the balance between dopamine and serotonin transmission.
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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:month |
Jun
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pubmed:issn |
0006-8993
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
759
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
205-12
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9221938-Animals,
pubmed-meshheading:9221938-Dopamine,
pubmed-meshheading:9221938-Ketamine,
pubmed-meshheading:9221938-Male,
pubmed-meshheading:9221938-Microdialysis,
pubmed-meshheading:9221938-Prefrontal Cortex,
pubmed-meshheading:9221938-Rats,
pubmed-meshheading:9221938-Rats, Sprague-Dawley,
pubmed-meshheading:9221938-Serotonin,
pubmed-meshheading:9221938-gamma-Aminobutyric Acid
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pubmed:year |
1997
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pubmed:articleTitle |
Differential effects of single and repeated ketamine administration on dopamine, serotonin and GABA transmission in rat medial prefrontal cortex.
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pubmed:affiliation |
Department of Clinical Neuroscience, Karolinska Institutet and Hospital, Stockholm, Sweden. nilsl@psyk.ks.se
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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