Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-3-24
pubmed:abstractText
Cocaine's ability to block the dopamine transporter (DAT) is crucial for its reinforcing effects. However the brain functional consequences of DAT blockade by cocaine are less clear since they are confounded by its concomitant blockade of norepinephrineand serotonin transporters. To separate the dopaminergic from the non-dopaminergic effects of cocaine on brain function we compared the regional brain metabolic responses to cocaine between dopamine transporter deficient (DAT(-/-)) mice with that of their DAT(+/+) littermates. We measured regional brain metabolism (marker of brain function) with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and microPET (muPET) before and after acute cocaine administration (i.p. 10 mg/kg). Scans were conducted 2 weeks apart. At baseline DAT(-/-) mice had significantly greater metabolism in thalamus and cerebellum than DAT(+/+). Acute cocaine decreased whole brain metabolismand this effect was greater in DAT(+/+) (15%) than in DAT(-/-) mice (5%). DAT(+/+) mice showed regional decreases in the olfactory bulb, motor cortex, striatum, hippocampus, thalamus and cerebellum whereas DAT(-/-) mice showed decreases only in thalamus. The differential pattern of regional responses to cocaine in DAT(-/-) and DAT(+/+) suggests that most of the brain metabolic changes from acute cocaine are due to DAT blockade. Cocaine-induced decreases in metabolism in thalamus (region with dense noradrenergic innervation) in DAT(-/-) suggest that these were mediated by cocaine's blockade of norepinephrine transporters. The greater baseline metabolism in DAT(-/-) than DAT(+/+) mice in cerebellum (brain region mostly devoid of DAT) suggests that dopamine indirectly regulates activity of these brain regions.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-10195128, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-10404198, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-10435196, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-10651856, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-11312315, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-11320258, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-11406324, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-117743, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-11981592, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-12196592, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-12359863, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-12411561, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-14624807, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-14668974, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-15050599, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-15166646, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-15987937, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-16205719, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-16451810, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-16459261, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-16754872, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-1719677, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-2350209, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-363301, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-3814665, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-7059797, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-7116159, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-8558251, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-8628395, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-864466, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-8743604, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-9276849, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-9520487, http://linkedlifedata.com/resource/pubmed/commentcorrection/18286542-9636213
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0887-4476
pubmed:author
pubmed:issnType
Print
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
319-24
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
The effects of cocaine on regional brain glucose metabolism is attenuated in dopamine transporter knockout mice.
pubmed:affiliation
Behavioral Neuropharmacology Lab, Medical Department, Brookhaven National Laboratory, Upton, New York 11973-5000, USA. thanos@bnl.gov
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural