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Direct approach for attenuating cocaine's effects on extracellular dopamine: Targeting the dopamine transporter
Author(s) -
Morgan Alexander E.,
Porter Simone P.,
Clarkson Francis A.,
Volkow Nora D.,
Fowler Joanna S.,
Dewey Stephen L.
Publication year - 1997
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199708)26:4<423::aid-syn10>3.0.co;2-u
Subject(s) - nucleus accumbens , microdialysis , dopamine transporter , dopamine , dopamine uptake inhibitors , pharmacology , extracellular , medicine , chemistry , dopaminergic , biochemistry
Using in vivo microdialysis techniques, the effects of RTI‐55 and/or cocaine on extracellular dopamine (DA) concentrations were measured in the nucleus accumbens (NACC) of freely moving rats. In control animals, cocaine (20 mg/kg) increased NACC DA approximately 458% 60 minutes following administration, returning to baseline values within 200 minutes. Similarly, RTI‐55 administration (0.25 mg/kg) increased NACC DA levels approximately 347%. When combined, however, cocaine further increased NACC DA to 705% of baseline values when given 4 hours following RTI‐55. This increase was significantly larger than cocaine alone ( P < 0.05). In addition, chronic RTI‐55 administration (5 days) further potentiated cocaine's ability to increase NACC DA (783%) but this did not reach statistical significance ( P > 0.1) compared to acute RTI55/cocaine animals. These findings indicate that RTI‐55, a drug that binds directly to the dopamine transporter (DAT) with higher affinity than cocaine, does not appear to be effective in attenuating cocaine's effects on NACC dopamine levels. In fact, acute RTI‐55 potentiates cocaine's effects on NACC DA. Synapse 26:423–427, 1997. Published 1997 Wiley‐Liss, Inc. This article is a US government work and, as such, is in the public domain of the United States of America.