Linked Life Data

11251190

Source:http://linkedlifedata.com/resource/pubmed/id/11251190

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-3-19
pubmed:abstractText
The interaction of glutamatergic and dopamine neurotransmission is thought to have relevance to both the pathophysiology and pharmacotherapy of schizophrenia. For example, subanesthetic doses of the N-methyl-D-aspartate receptor (NMDA-R) antagonist ketamine induce schizophrenia-like behavioral effects in humans and both behavioral and brain metabolic activation in rodents. Blockade of NMDA-R results in dopamine release, and antipsychotic drugs that block dopamine neurotransmission decrease NMDA-R antagonist-induced behavioral activation. The involvement of dopamine receptors in brain metabolic activation induced by ketamine is, however, unknown. The present study used D(1A) knockout mice to determine the role of dopamine D(1A) receptors in the effects of subanesthetic doses of ketamine on both behavioral responses and on alterations in regional [14C]2-deoxyglucose (2-DG) uptake. There was less ketamine-induced behavioral activation in D(1A) knockout mice than in wild-type mice. In wild-type mice, ketamine (30 mg/kg) induced dramatic increases in 2-DG uptake in limbic cortical regions, hippocampal formation, nucleus accumbens, basolateral amygdala, and caudal parts of the substantia nigra pars reticulata. D(1A) knockout mice exhibited blunted metabolic activation in response to ketamine in a neuroanatomically specific manner. The selective D(1) antagonist, SCH23390 (0.3 mg/kg), inhibited both ketamine-induced brain metabolic activation and behavioral responses in the wild-type mice, with a similar neuroanatomical specificity observed in the D(1A) knockout mice. Thus, the neuroanatomically selective role that D(1A) receptors play in ketamine-induced behavior and regional brain metabolic activation in mice provides a useful model for further studies of how the D(1A) receptor function may be altered in schizophrenia.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
894
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
167-80
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Blunted brain metabolic response to ketamine in mice lacking D(1A) dopamine receptors.
pubmed:affiliation
Department of Psychiatry, University of North Carolina, School of Medicine, Chapel Hill, NC 27599, USA. seiya.miyamoto@css.unc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.