Linked Life Data

16206183

Source:http://linkedlifedata.com/resource/pubmed/id/16206183

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-10-10
pubmed:abstractText
Dopaminergic mechanisms are thought to play a central role in the reinforcing effects of cocaine. Similar to cocaine, other local anesthetics bind to the dopamine transporter (DAT) and inhibit DA uptake in rodent and monkey brain. Additionally, local anesthetics are self-administered in rhesus monkeys, indicative of abuse liability. The present study examined the reinforcing and DAT effects of the local anesthetics dimethocaine, procaine and cocaine using in vivo techniques. Monkeys were trained to respond under a second-order schedule for i.v. cocaine administration (0.10 or 0.30 mg/kg/infusion). When responding was stable, dimethocaine (0.030-1.7 mg/kg/ infusion) or procaine (0.10-10 mg/kg/ infusion) was substituted for the cocaine training dose. Dimethocaine administration produced higher response rates compared with that of procaine, and was a more potent reinforcer. Drug effects on behavior were related to DAT occupancy in monkey striatum during neuroimaging with positron emission tomography (PET). DAT occupancy was determined by displacement of 8-(2-[(18)F]fluroethyl)2beta-carbomethoxy-3beta-(4-chlorophenyl)nortropane (FECNT). DAT occupancy was between 66 and 82% and <10-41% for doses of dimethocaine and procaine that maintained maximum response rates, respectively. Finally, in vivo microdialysis in awake subjects determined drug-induced changes in extracellular DA in the caudate nucleus. There was close correspondence between peak increases in DA and DAT occupancy. Overall, reinforcing effects were consistent with DAT effects determined with in vivo techniques. The results further support a role for the DAT in the abuse liability of local anesthetics.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0887-4476
pubmed:author
pubmed:copyrightInfo
Copyright 2005 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
220-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
In vivo comparison of the reinforcing and dopamine transporter effects of local anesthetics in rhesus monkeys.
pubmed:affiliation
Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural