Abstract
Stimulant misuse is strongly associated with behavioral impulsivity, including impairments in behavioral inhibition, yet few studies have examined drug self-administration in ways that directly assess inhibitory control. This study aimed to discover if intravenous (IV) self-administration of cocaine and d-amphetamine could be established using a differential reinforcement of low rates (DRL) schedule in rats and whether stimulant intake altered behavioral inhibition. Male Sprague-Dawley rats were trained to lever press under DRL schedules with food reinforcement, then transitioned to IV cocaine (0.3 mg/kg/infusion) or d-amphetamine (0.06 mg/kg/infusion) self-administration sessions. Following the acquisition, full dose-effect curves were established with cocaine (DRL > 10 s) and d-amphetamine (DRL > 7 s), resulting in inverted-U-shaped curves for both active lever presses and infusions earned. The most active lever presses occurred at the second-highest dose for cocaine (0.3 mg/kg/infusion) and d-amphetamine (0.02 mg/kg/infusion). Analysis of cumulative probabilities of interresponse times (IRTs) revealed drug-specific effects on behavioral inhibition. At peak cocaine intake (0.1 mg/kg/infusion), approximately 65% of lever presses occurred before the DRL 10 s requirement, indicating a failure to inhibit responses. In contrast, at the highest (0.06 mg/kg/infusion) and lowest (0.006 mg/kg/infusion) doses of d-amphetamine self-administration, we observed increased long IRTs beyond the 300 s limited hold contingency, similar to saline. These findings demonstrate rats will self-administer stimulants under a DRL schedule, and cocaine and d-amphetamine differentially disrupt behavioral inhibition. This approach provides novel insight into the complex relationships between stimulant use and behavioral control and provides a foundation for future investigations into the mechanisms of behavioral inhibition.