Cocaine and d-amphetamine self-administration under a differential reinforcement of low rates schedule of reinforcement in rats.

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.