Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8350801 | Pharmacology Biochemistry and Behavior | 2015 | 8 Pages |
Abstract
The Na+-dependent dopamine transporter (DAT) is primarily responsible for regulating free dopamine (DA) concentrations in the brain by participating in the majority of DA uptake; however, other DA transporters may also participate, especially if cocaine or other drugs of abuse compromise DAT. Recently, such cocaine-insensitive low-affinity mono- and poly-amine OCT transporters were described in astrocytes which use DA as a substrate. These transporters are from a different transporter family and while insensitive to cocaine, they are specifically blocked by quinine and some steroids. Quinine is inexpensive and is often found in injected street drugs as an “adulterant”. The present study was designed to determine the participation of OCTs in cocaine dependent behavioral and physiological changes in mice. Using FVB mice we showed, that daily single injections of quinine (10Â mg/kg, i.p.) co-administered with cocaine (15Â mg/kg, i.p.) for 10Â days significantly enhanced cocaine-induced locomotor behavioral sensitization. Quinine had no significant effect on the time course of behavioral activation. In astrocytes from the ventral tegmental area of mice, transporter currents of quinine-sensitive monoamine transporters were also augmented after two weeks of cocaine administration. The importance of low-affinity high-capacity transporters for DA clearance is discussed, explaining the known ability of systemically administered DAT inhibitors to anomalously increase DA clearance.
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Adriana Huertas, William D. Wessinger, Yuri V. Kucheryavykh, Priscila Sanabria, Misty J. Eaton, Serguei N. Skatchkov, Legier V. Rojas, Gerónimo Maldonado-MartÃnez, Mikhail Y. Inyushin,