Linked Life Data

12244091

Source:http://linkedlifedata.com/resource/pubmed/id/12244091

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 10
pubmed:dateCreated
2002-9-23
pubmed:abstractText
Dopamine and glutamate are key neurotransmitters in cortico-basal ganglia loops affecting motor and cognitive function. To examine functional convergence of dopamine and glutamate neurotransmitter systems in the basal ganglia, we evaluated the long-term effects of chronic stimulation of each of these systems on striatal responses to stimulation of the other. First we exposed rats to chronic intermittent cocaine and used early-gene assays to test the responsivity of the striatum to subsequent acute motor cortex stimulation by application of the GABA(A) (gamma-aminobutyric acid alpha subunit) receptor antagonist, picrotoxin. Reciprocally, we studied the effects of chronic intermittent motor cortex stimulation on the capacity for subsequent acute dopaminergic treatments to induce early-gene activation in the striatum. Prior treatment with chronic intermittent cocaine induced motor sensitization and significantly potentiated the striatal expression of Fos-family early genes in response to stimulation of the motor cortex. Contrary to this, chronic intermittent stimulation of the motor cortex down-regulated cocaine-induced gene expression in the striatum, but enhanced striatal gene expression induced by a full D1 receptor agonist (SKF 81297) and did not change the early-gene response elicited by a D2 receptor antagonist (haloperidol). These findings suggests that repeated dopaminergic stimulation produces long-term enhancement of corticostriatal signalling from the motor cortex, amplifying cortically evoked modulation of the basal ganglia. By contrast, persistent stimulation of the motor cortex inhibits cocaine-stimulated signalling in the striatum, but not signalling mediated by individual dopamine receptor sites, suggesting that chronic cortical hyperexcitability produces long-term impairment of dopaminergic activity and compensation at the receptor level. These findings prompt a model of the basal ganglia function as being regulated by opposing homeostatic dopamine-glutamate neurotransmitter interactions. The model provides a framework for analysing the neurological alterations associated with disorders of the basal ganglia and their treatment with pharmacotherapies affecting dopamine and glutamate neurotransmitter systems.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-8950
pubmed:author
pubmed:issnType
Print
pubmed:volume
125
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2353-63
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Shifts in striatal responsivity evoked by chronic stimulation of dopamine and glutamate systems.
pubmed:affiliation
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 45 Carleton Street, Cambridge, MA 02139, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't