Reinforcing Doses of Intravenous Cocaine Produce Only Modest Dopamine Uptake Inhibition.
ACS Chem Neurosci
; 8(2): 281-289, 2017 02 15.
Article
em En
| MEDLINE
| ID: mdl-27936579
ABSTRACT
The reinforcing efficacy of cocaine is thought to stem from inhibition of the dopamine transporter (DAT) and subsequent increases in extracellular dopamine concentrations in the brain. In humans, this hypothesis has generally been supported by positron emission tomography imaging studies where the percent of DATs occupied by cocaine is used as a measure of cocaine activity in the brain. Interpretation of these studies, however, often relies on the assumption that measures of DAT occupancy directly correspond with functional DAT blockade. In the current studies, we used in vivo and in vitro fast scan cyclic voltammetry in mice to measure dopamine uptake inhibition following varying doses of cocaine as well as two high affinity DAT inhibitors. We then compared dopamine clearance rates following these drug treatments to dopamine clearance obtained from DAT knockout mice as a proxy for complete DAT blockade. We found that administration of abused doses of cocaine resulted in approximately 2% of maximal DAT blockade. Overall, our data indicate that abused doses of cocaine produce a relatively modest degree of DA uptake inhibition, and suggest that the relationship between DAT occupancy and functional blockade of the DAT is more complex than originally posited.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Reforço Psicológico
/
Dopamina
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Cocaína
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Área Tegmentar Ventral
Limite:
Animals
Idioma:
En
Revista:
ACS Chem Neurosci
Ano de publicação:
2017
Tipo de documento:
Article