Cocaine, as a powerful psychostimulant, has high abuse potentials. Cocaine addiction, usually developing after repeated cocaine use, can lead to declined health and inability to perform in daily lives. According to the 2014 National Survey on Drug Use and Health, nearly 1 million Americans were diagnosed with cocaine dependence within the past year. A major challenge in treating cocaine addiction is relapse during abstinence, which is commonly triggered by exposure to cues and other stimuli previously associated with cocaine use [1]. In both rats and humans, cue-induced cocaine seeking progressively increases after withdrawal, a phenomenon termed “incubation of cocaine craving” [2].

Among people who have experienced cocaine, not everyone develops addiction. A key factor that contributes to the abuse liability is the temporal profile of cocaine use, which includes the intermittency (e.g., binge-taking sessions with long-intervals in between) and the rate of cocaine delivery [3]. Clinical observations have shown that rapid routes of cocaine administration (e.g., smoking and intravenous injection), which leads to high plasma concentration of cocaine within 2–5 min, facilitates the transition from controlled drug use to compulsive drug-taking behavior, a major characteristic of drug addiction [4]. Preclinical studies using rats have also demonstrated that rapid cocaine delivery promotes cocaine-induced behavioral effects, including locomotor sensitization, incentive motivation, escalation of cocaine intake, and cocaine-primed reinstatement of cocaine seeking [3, 5]. However, a key question remained unanswered: does rapid cocaine injection promote incubation of cocaine craving?

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