Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2003-12-19
pubmed:abstractText
A variety of data point to the possibility that neuroadaptations in glutamate transmission are produced by repeated exposure to cocaine that result in the expression of behaviors characteristic of addiction, such as craving and relapse. Using the reinstatement model of relapse in rats, glutamate release in the projection from the prefrontal cortex to the nucleus accumbens has been shown to underlie cocaine- and stress-primed reinstatement. In this report, four adaptations produced by withdrawal from repeated cocaine are described that may regulate the release of glutamate underlying reinstatement of drug-seeking resulted. (1) Neurons in the prefrontal cortex have increased levels of activator of G protein signaling 3 (AGS3) that causes reduced signaling through Gi coupled receptors, and normalization of AGS3 blocked cocaine-primed reinstatement. (2) The activity of the cystine-glutamate exchanger is reduced resulting in decreased extracellular glutamate in the nucleus accumbens, and normalization of exchanger activity prevented cocaine-primed reinstatement. (3) Metobotropic glutamate receptor function is diminished after repeated cocaine administration that results in reduced regulation of glutamate release. (4) Homer1 protein is reduced in the nucleus accumbens, and Homer2 knockout mice show enhanced responsiveness to cocaine. Taken together, there appears to be both pre- and postsynaptic changes in glutamate transmission that dysregulates the glutamatergic projection from the prefrontal cortex to the nucleus accumbens. These adaptations are hypothesized to facilitate glutamate release in response to a cocaine injection or acute stress and lead to the reinstatement of drug-seeking behavior.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0077-8923
pubmed:author
pubmed:issnType
Print
pubmed:volume
1003
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
169-75
pubmed:dateRevised
2011-7-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Glutamate transmission and addiction to cocaine.
pubmed:affiliation
Department of Physiology and Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29464, USA. kalivasp@musc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.