title: Quinine enhances the behavioral stimulant effect of cocaine in mice.
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 (10 mg/kg, i.p.) co-administered with cocaine (15 mg/kg, i.p.) for 10 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.
authors.affiliation: Univ. Central del Caribe, Bayamón, Puerto Rico. Electronic address: adrish6016@gmail.com.
authors.forename: Adriana
authors.initials: A
authors.lastname: Huertas
authors.affiliation: Univ. of Arkansas for Medical Science, Little Rock, AR, United States. Electronic address: wdwessinger@uams.edu.
authors.forename: William D
authors.initials: WD
authors.lastname: Wessinger
authors.affiliation: Univ. Central del Caribe, Bayamón, Puerto Rico. Electronic address: yuriy.kucheryavykh@uccaribe.edu.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Kucheryavykh
authors.affiliation: Univ. Central del Caribe, Bayamón, Puerto Rico. Electronic address: psanabriar@gmail.com.
authors.forename: Priscila
authors.initials: P
authors.lastname: Sanabria
authors.affiliation: Univ. Central del Caribe, Bayamón, Puerto Rico. Electronic address: mistyeaton1960@yahoo.com.
authors.forename: Misty J
authors.initials: MJ
authors.lastname: Eaton
authors.affiliation: Univ. Central del Caribe, Bayamón, Puerto Rico. Electronic address: sergueis50@yahoo.com.
authors.forename: Serguei N
authors.initials: SN
authors.lastname: Skatchkov
authors.affiliation: Univ. Central del Caribe, Bayamón, Puerto Rico. Electronic address: lrojas@uccaribe.edu.
authors.forename: Legier V
authors.initials: LV
authors.lastname: Rojas
authors.affiliation: Univ. Central del Caribe, Bayamón, Puerto Rico. Electronic address: geronimo.maldonado@uccaribe.edu.
authors.forename: Gerónimo
authors.initials: G
authors.lastname: Maldonado-Martínez
authors.affiliation: Universidad Central del Caribe, School of Medicine, P.O. Box 60-327, Bayamón 00960-6032, Puerto Rico. Electronic address: mikhail.inyushin@uccaribe.edu.
authors.forename: Mikhail Y
authors.initials: MY
authors.lastname: Inyushin
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004357:Drug Synergism; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D011803:Quinine / Q000494:pharmacology*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D011803:Quinine; D003042:Cocaine; D004298:Dopamine
keywords: Dopamine; Locomotor behavioral activation; Low affinity transporters; Quinine; Transporter current