Extended access to amphetamine self-administration increases impulsive choice in a delay discounting task in rats

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Abstract
D-Amphetamine (AMPH) is a widely prescribed attention deficit hyperactivity disorder medication, but little is known about its effects on impulsive choice with escalated use. The current study examined the effects of short and long access to AMPH self-administration on impulsive choice in a delay discounting task in which rats chose between a small immediate reward (one sucrose pellet immediately) and a larger delayed reward (three sucrose pellets after an adjusting delay). Following choice stability in delay discounting, all rats received 15 1-h sessions of AMPH self-administration (0.1 or 0.03 mg/kg/infusion); self-administration sessions began 45 min after each delay discounting session. Rats were then either maintained on the short access (ShA) self-administration session or were switched to a long access (LgA) 6-h session for 21 days, followed by a 7-day withdrawal phase in which only the delay discounting task continued. LgA rats in the 0.03 mg/kg/infusion dose group escalated in total number of infusions across sessions, although rats in the 0.1 mg/kg/infusion dose group did not. LgA groups at both unit doses showed decreased mean adjusted delays across sessions compared to the ShA groups, indicating that long access to AMPH increases impulsive choice. During the AMPH withdrawal phase, LgA groups returned back to baseline mean adjusted delays, indicating that the effect on impulsive choice was reversible. These results show that extended AMPH self-administration produces a transient loss of inhibitory control, which may play a role in the escalating pattern of drug intake that characterizes the addiction process.