Substantial evidence implicates dopamine as the primary neurotransmitter system involved in the rewarding effects of cocaine exposure (Dackis & Gold, 1985; Haile et al., 2007; Kuhar et al., 1991). Cocaine competitively inhibits dopamine internalization by binding to the dopamine transporter (Beuming et al., 2008). Administration of a typical dose (i.e., what a user might be expected to take) in humans blocks a majority of dopamine transporter sites (Volkow et al., 1997). The blocking of these sites results in increased synaptic dopamine, which contributes to the reinforcing and addictive properties of cocaine (Haile et al., 2007). Cocaine exposure induces long-term potentiation of dopamine neurons (Lin et al., 2005; Ungless et al., 2001). Extended use results in persisting effects on nuclear accumbens D1 receptors (Henry & White, 1991) and prefrontal dopamine D2 receptors (Briand et al., 2008).
