Thus, when the mechanisms underlying the rewarding and reinforcing effects of cocaine were first considered in knockout mice, expectations were based upon a preponderance of data indicating that dopamine was the primary mediator of the rewarding effects of cocaine, despite the fact that cocaine inhibits reuptake via the serotonin transporter (SERT) and the norepinephrine transporter (NET) as well (Rothman & Baumann, 2003). This was supported by an apparent correlation between reinforcing efficacy and the ability of various compounds to bind to DAT (Kuhar, Ritz, & Boja, 1991). Thus, the first publication examining the behavioral effects of cocaine in DAT KO mouse described these mice as being “indifferent” to cocaine (Giros, Jaber, Jones, Wightman, & Caron, 1996), consistent with expectations. This was based upon the observation that DAT KO mice did not exhibit locomotor stimulant effects of cocaine. However, subsequent studies demonstrated that DAT KO mice could develop both a conditioned place preference for cocaine and self-administer cocaine, at least under some conditions, using strains developed at the the Molecular Neurobiology Branch (MNB) at the National Institute on Drug Abuse, (USA)
