Cocaine withdrawal alters the reward omission effect and enhances traits of negative urgency in rats across multiple days of testing

• Withdrawal from binge cocaine in rats increases markers of negative urgency in a reward-omission task.
• The effects of cocaine on negative urgency are dose- and time-dependent.
• RTI-113, a selective inhibitor of the dopamine transporter, does not mimic the effects of cocaine.

BackgroundThe personality trait of negative urgency, characterized as behaving rashly when emotionally perturbed, is gaining attention as an indicator for susceptibility to problematic substance use. How this trait is influenced by exposure to drugs of abuse is still unclear. Using an animal model of binge cocaine consumption, we tested this relationship in a reward-omission task across multiple days.MethodsAdult, male, Sprague-Dawley rats received seven daily (ip) injections of saline, cocaine (10–20 mg/kg), or cocaine (20–40 mg/kg). Cocaine doses increased linearly each day from the lower to the higher dose. A separate group received RTI-113 (3.0 mg/kg), a selective dopamine transporter inhibitor, for 7 days. Fifteen days after their final injection, rats were trained on a reward-omission task with an operant component to earn further rewards.ResultsPrevious exposure to cocaine resulted in dose-dependent increases in negative urgency in separate behavioral variables across days of testing. The lower dose range increased negative urgency on the dimension of decreased reaction time to press a lever, while the higher dose range increased the rate of increase in lever presses made per trial. Rats receiving RTI-113 did not resemble either cocaine group and instead showed a decrease in lever pressing across days.ConclusionsOur results indicate that previous binge cocaine consumption enhances behavioral markers of negative urgency in a dose-dependent, time-sensitive manner on discrete behavioral dimensions. The results with RTI-113 suggest the relationship between cocaine exposure and negative urgency is unlikely to be explained solely by inhibition of dopamine reuptake.